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Ali A, Younas K, Khatoon A, Murtaza B, Ji Z, Akbar K, Tanveer Q, Bahadur SUK, Su Z. Immune watchdogs: Tissue-resident lymphocytes as key players in cancer defense. Crit Rev Oncol Hematol 2025; 208:104644. [PMID: 39900319 DOI: 10.1016/j.critrevonc.2025.104644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 01/27/2025] [Accepted: 01/29/2025] [Indexed: 02/05/2025] Open
Abstract
Tissue-resident lymphocytes play a crucial role in immune surveillance against cancer, yet their complex interactions and regulatory pathways remain underexplored, highlighting the need for a deeper understanding to enhance cancer immunotherapy strategies. Lymphocytes across the range of innate-adaptive responses can establish long-lasting presence in tissues, exerting a vital function in the local immune response against diverse antigens. These tissue-resident lymphocytes identify antigens and alarmins secreted by microbial infections and non-infectious stresses at barrier locations by closely interacting with epithelial and endothelial cells. Then they initiate effector responses to restore tissue homeostasis. Significantly, this immune defense system has been demonstrated to monitor the processes of epithelial cell transformation, carcinoma advancement, and cancer metastasis at remote locations, so establishing it as an essential element of cancer immunological surveillance. This review aims to elucidate the roles of diverse tissue-resident lymphocyte populations in shaping cancer immune responses and to investigate their synergistic effector mechanisms for advancing cancer immunotherapy.
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Affiliation(s)
- Ashiq Ali
- Department of Histology and Embryology, Shantou University Medical College, Shantou, China.
| | - Khadija Younas
- Department of Theriogenology, University of Agriculture, Faisalabad, Pakistan
| | - Aisha Khatoon
- Department of Pathology, University of Agriculture, Faisalabad, Pakistan
| | - Bilal Murtaza
- Dalian University of Science and Technology, Dalian, China
| | - Ziyi Ji
- Department of Histology and Embryology, Shantou University Medical College, Shantou, China
| | - Kaynaat Akbar
- Department of Zoology, Wildlife and Fisheries, Faculty of Sciences, University of Agriculture, Faisalabad, Pakistan
| | - Qaisar Tanveer
- The Roslin Institute, The Royal (Dick) School of Veterinary Studies, The University of Edinburgh, EH25 9RG, UK
| | - Sami Ullah Khan Bahadur
- College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Colins, CO 80523, USA
| | - Zhongjing Su
- Department of Histology and Embryology, Shantou University Medical College, Shantou, China.
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Hassan MI, Hassan SS, Soliman FNK, Khalil MH. Effects of In Ovo Administration of Freeze-Dried Royal Jelly on Hatchability, Blood Parameters, and Organ Weights of Day-Old Chicks. J Anim Physiol Anim Nutr (Berl) 2025; 109:259-267. [PMID: 39369274 DOI: 10.1111/jpn.14052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 09/11/2024] [Accepted: 09/19/2024] [Indexed: 10/07/2024]
Abstract
Royal jelly renowned for its robust nutritional, functional, and biological properties, is a pivotal product derived from honeybees. The purpose of this investigation was to assess the theory that in ovo injection of freeze-dried royal jelly (FDRJ) solutions at varying concentrations can influence the hatchability, blood properties and hatching characteristics of day-old chicks. A total of 480 eggs (54.81 ± 0.187 g) were allocated into four experimental groups: negative control (NC), without injection, positive control (PC), administered with regular saline, a low FDRJ dose group (9 mg/egg), and a high FDRJ dose group (18 mg/egg). The in ovo injections were administered on Day 18 of incubation, and the experiment was subsequently continued until the incubation period concluded at 21 days. Results revealed that the lower FDRJ dose (9 mg/egg) significantly improved hatchability percentages compared to other treatments. Conversely, the higher FDRJ dose (18 mg/egg) and control groups (NC and PC) resulted in significantly higher chick yield percentages than the lower FDRJ and PC groups. The NC group showed the supreme yolk sac (YS) percentage, whereas the yolk-free body mass (YFBM) percentages displayed an inverse trend. Furthermore, the in ovo FDRJ injection did not affect haematological values or the relative organ weight of day-old chicks. In conclusion, in ovo FDRJ injection demonstrated beneficial effects on hatchability and chick weight, as evidenced by the studied parameters.
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Affiliation(s)
- Mohamed I Hassan
- Livestock Research Department, Arid Lands Cultivation Research Institute, City of Scientific Research and Technological Applications (SRTA-City), New Borg El-Arab, Alexandria, Egypt
| | - Saber S Hassan
- Animal and Poultry Production Department, Faculty of Agriculture, Damanhour University, Damanhour, Egypt
| | - Farid N K Soliman
- Poultry Production Department, Faculty of Agriculture, Alexandria University, Alexandria, Egypt
| | - Mohamed H Khalil
- Poultry Production Department, Faculty of Agriculture, Alexandria University, Alexandria, Egypt
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3
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Sandmeier FC, Olson K, Martin A, Urban T. Memory responses to ovalbumin-immunization in Mojave desert tortoises. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2025; 164:105322. [PMID: 39880345 DOI: 10.1016/j.dci.2025.105322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 12/30/2024] [Accepted: 01/19/2025] [Indexed: 01/31/2025]
Abstract
We immunized three groups of Mojave desert tortoises (Gopherus agassizii): a group immunized twice, a group immunized once, and a group sham-immunized. We used the antigen, ovalbumin (OVA), with Freund's adjuvant to elicit antibody responses similar to those induced by extracellular bacteria. All tortoises have relatively high levels of B1 lymphocytes and natural antibodies (NAbs), and the goal of this study was to quantify B2 lymphocyte activity (antibody production and potential proliferation) that occurs in primary and secondary immunizations against this constitutive, first line of humoral defense. Specifically, we were testing for two types of induced, immunological memory. These included an elevated long-term increase in OVA-specific induced antibodies as well as for features of B2 memory cells, such as increased numbers of circulating OVA-specific cells, increased antibody production and avidity, and proliferation in the presence of OVA. Secondary responses were faster, but without any increases in antibody titer or avidity. Both groups had long-term elevation in antibodies. Over all three groups, we found no effect of the immunization (pre-vs-post) or the number of immunizations (0, 1, 2) on the number of OVA-stimulated B cells. We found an effect of immunization, but not number of immunizations, on the amount of antibody secreted by B lymphocytes. This suggests a high constitutive level of circulating B1 lymphocytes that can be stimulated by immunization. We did not find evidence of B2 memory lymphocytes because cells could not be stimulated to proliferate. Control animals confirmed that NAbs increased due to B1 lymphocyte priming with adjuvant.
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Affiliation(s)
- Franziska C Sandmeier
- Biology Department, University of Colorado - Pueblo, 2200 Bonforte Ave., Pueblo, CO, 81001, USA.
| | - Kiara Olson
- Biology Department, University of Colorado - Pueblo, 2200 Bonforte Ave., Pueblo, CO, 81001, USA
| | - Angelina Martin
- Biology Department, University of Colorado - Pueblo, 2200 Bonforte Ave., Pueblo, CO, 81001, USA
| | - Taylor Urban
- Biology Department, University of Colorado - Pueblo, 2200 Bonforte Ave., Pueblo, CO, 81001, USA
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4
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Tian X, Liu Y, Zhu K, An H, Feng J, Zhang L, Zhang JR. Natural antibodies to polysaccharide capsules enable Kupffer cells to capture invading bacteria in the liver sinusoids. J Exp Med 2025; 222:e20240735. [PMID: 39718543 DOI: 10.1084/jem.20240735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 09/23/2024] [Accepted: 11/25/2024] [Indexed: 12/25/2024] Open
Abstract
The interception of blood-borne bacteria in the liver defines the outcomes of invasive bacterial infections, but the mechanisms of this antibacterial immunity are not fully understood. This study shows that natural antibodies (nAbs) to capsules enable liver macrophage Kupffer cells (KCs) to rapidly capture and kill blood-borne encapsulated bacteria in mice. Affinity pulldown with serotype-10A capsular polysaccharides (CPS10A) of Streptococcus pneumoniae (Spn10A) led to the identification of CPS10A-binding nAbs in serum. The CPS10A-antibody interaction enabled KCs to capture Spn10A bacteria from the bloodstream, in part through complement receptors on KCs. The nAbs were found to recognize the β1-6-linked galactose branch of CPS10A and similar moieties of serotype-39 S. pneumoniae and serotype-K50 Klebsiella pneumoniae capsules. More importantly, the nAbs empowered KCs to capture serotype-39 S. pneumoniae and serotype-K50 K. pneumoniae in the liver. Collectively, our data have revealed a highly effective immune function of nAb against encapsulated bacteria and emphasize the concept of treating septic encapsulated bacterial diseases with monoclonal antibodies.
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Affiliation(s)
- Xianbin Tian
- School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University , Beijing, China
| | - Yanni Liu
- School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University , Beijing, China
- Tsinghua-Peking Center for Life Sciences, Tsinghua University , Beijing, China
| | - Kun Zhu
- School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University , Beijing, China
| | - Haoran An
- School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University , Beijing, China
- Institute of Medical Technology, Peking University Health Science Center , Beijing, China
- Department of Microbiology and Infectious Disease Center, Peking University Health Science Center, Beijing, China
| | - Jie Feng
- State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
| | - Linqi Zhang
- School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University , Beijing, China
| | - Jing-Ren Zhang
- School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University , Beijing, China
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5
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Zhang Z, Yu C, Chen Z, Hou P, Sun J, Yang C, Tian Y, Yang Z, Yang Y, Shang S. Holstein × Montbéliarde-sired F1 generation crossbred female calves have an increased cellular immune response potential compared with purebred Holsteins. Vet Q 2024; 44:1-10. [PMID: 39625805 PMCID: PMC11616738 DOI: 10.1080/01652176.2024.2435982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 11/20/2024] [Accepted: 11/24/2024] [Indexed: 12/06/2024] Open
Abstract
It is well known that crossbreds show many advantages over purebreds in improving calf health traits, but the immunological factors responsible for this heterosis remain largely unclear. The objective of this study was to compare the cellular immune responses and antibodies of Holstein (HO) and Montbéliarde-sired × Holstein (MH) F1 generation female calves, and investigate the effects of crossbreeding on the immunity. Fifty three-month-old healthy female calves (25 HO, 25 MH) were selected meticulously in a farm with the same criteria. Subsequently, complete blood count, flow cytometric analysis of T cell subsets and intracellular IFN-γ production, as well as indirect ELISA analysis of antibodies were performed in order to determine the immune profiles of the two groups of calves. We found that MH calves had higher percentage and number of CD4+ and CD8+ T cells than HO calves in the peripheral blood (p < 0.05), with higher MFI of CD44 on CD4+ and CD8+ T cells (p < 0.05). When stimulated by PMA and Ionomycin, the CD4+ and CD8+ T cells from MH calves secreted more IFN-γ than that of HO calves (p < 0.01). These results suggested that some immunological traits have been improved in MH calves, which may be an important cause of heterosis in crossbred animals.
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Affiliation(s)
- Zhipeng Zhang
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, China
| | - Chen Yu
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Zhi Chen
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Ping Hou
- School of Nursing & School of Public Health, Yangzhou University, Yangzhou, China
| | - Jie Sun
- Shenzhen Academy of Inspection and Quarantine Sciences, Shenzhen, China
| | - Chunhua Yang
- Institute of Biological Resources, Jiangxi Academy of Sciences, Nanchang, China
| | - Yu Tian
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Zhangping Yang
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
- Joint International Research Laboratory of Agriculture & Agri-Product Safety, Ministry of Education, Yangzhou University, Yangzhou, China
| | - Yi Yang
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, China
- Joint International Research Laboratory of Agriculture & Agri-Product Safety, Ministry of Education, Yangzhou University, Yangzhou, China
| | - Shaobin Shang
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, China
- Joint International Research Laboratory of Agriculture & Agri-Product Safety, Ministry of Education, Yangzhou University, Yangzhou, China
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Yang Y, Treger RS, Hernandez-Bird J, Lu P, Mao T, Iwasaki A. A B cell screen against endogenous retroviruses identifies glycan-reactive IgM that recognizes a broad array of enveloped viruses. Sci Immunol 2024; 9:eadd6608. [PMID: 39514636 PMCID: PMC11962862 DOI: 10.1126/sciimmunol.add6608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Accepted: 10/11/2024] [Indexed: 11/16/2024]
Abstract
Endogenous retroviruses (ERVs), comprising a substantial portion of the vertebrate genome, are remnants of ancient genetic invaders. ERVs with near-intact coding potential reactivate in B cell-deficient mice. To study how B cells contribute to host anti-ERV immunity, we used an antigen-baiting strategy to enrich B cells reactive to ERV surface antigens. We identified ERV-reactive B-1 cells expressing germline-encoded natural IgM antibodies in naïve mice, the level of which further increases upon innate immune sensor stimulation. B cell receptor repertoire profiling of ERV-reactive B-1 cells revealed increased usage of the Igh VH gene that gives rise to glycan-specific antibodies targeting terminal N-acetylglucosamine moieties on ERV glycoproteins, which further engage the complement pathway to mediate anti-ERV responses. These same antibodies also recognize glycoproteins of other enveloped viruses but not self-proteins. These results reveal an innate antiviral mechanism of germline-encoded antibodies with broad reactivity to enveloped viruses, which constitutes a natural antibody repertoire capable of preventing the emergence of infectious ERVs.
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Affiliation(s)
- Yexin Yang
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Rebecca S. Treger
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Juan Hernandez-Bird
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Peiwen Lu
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Tianyang Mao
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Akiko Iwasaki
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
- Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA
- Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA
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7
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New JS, Fucile CF, Callahan AR, Burke JN, Davis RS, Duck WL, Rosenberg AF, Kearney JF, King RG. Human Anti-Glycan Reactivity is Driven by the Selection of B cells Utilizing Private Antibody Gene Rearrangements that are Affinity Maturated in Germinal Centers. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.10.15.618486. [PMID: 39464096 PMCID: PMC11507706 DOI: 10.1101/2024.10.15.618486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 10/29/2024]
Abstract
The human antibody repertoire is broadly reactive with carbohydrate antigens represented in the universe of all living things, including both the host/self- as well as the commensal microflora-derived glycomes. Here we have used BCR receptor cloning and expression together with single-cell transcriptomics to analyze the B cell repertoire to the ubiquitous N-acetyl-D-glucosamine (GlcNAc) epitope in human cohorts and dissect the immune phylogeny of this predominant class of antibodies. We find that circulating anti-GlcNAc B cells exhibiting canonical BMem phenotypes emerge rapidly after birth and couple this observation with evidence for germinal center-dependent affinity maturation of carbohydrate-specific B cell receptors in situ during early childhood. Direct analysis of individual B cell clonotypes reveals they exhibit strikingly distinct fine-specificity profiles for palettes of GlcNAc containing moieties. These results suggest that a generalized exposure to complex environmental glycans drives the steady state anti-glycan repertoire.
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Affiliation(s)
- J. Stewart New
- Department of Microbiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham AL 35294, USA
| | - Christopher F. Fucile
- Informatics Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Amanda R. Callahan
- Department of Microbiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham AL 35294, USA
| | - Julia N. Burke
- Department of Microbiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham AL 35294, USA
| | - Randall S. Davis
- Department of Medicine, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL 35294, USA
| | - Wayne L. Duck
- Department of Medicine, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL 35294, USA
| | | | - John F. Kearney
- Department of Microbiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham AL 35294, USA
| | - R. Glenn King
- Department of Microbiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham AL 35294, USA
- Lead Contact
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8
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Weston K, Fulton JE, Owen J. Antigen specificity affects analysis of natural antibodies. Front Immunol 2024; 15:1448320. [PMID: 39170611 PMCID: PMC11335478 DOI: 10.3389/fimmu.2024.1448320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 07/22/2024] [Indexed: 08/23/2024] Open
Abstract
Natural antibodies are used to compare immune systems across taxa, to study wildlife disease ecology, and as selection markers in livestock breeding. These immunoglobulins are present prior to immune stimulation. They are described as having low antigen specificity or polyreactive binding and are measured by binding to self-antigens or novel exogenous proteins. Most studies use only one or two antigens to measure natural antibodies and ignore potential effects of antigen specificity in analyses. It remains unclear how different antigen-specific natural antibodies are related or how diversity among natural antibodies may affect analyses of these immunoglobulins. Using genetically distinct lines of chickens as a model system, we tested the hypotheses that (1) antigen-specific natural antibodies are independent of each other and (2) antigen specificity affects the comparison of natural antibodies among animals. We used blood cell agglutination and enzyme-linked immunosorbent assays to measure levels of natural antibodies binding to four antigens: (i) rabbit erythrocytes, (ii) keyhole limpet hemocyanin, (iii) phytohemagglutinin, or (iv) ovalbumin. We observed that levels of antigen specific natural antibodies were not correlated. There were significant differences in levels of natural antibodies among lines of chickens, indicating genetic variation for natural antibody production. However, line distinctions were not consistent among antigen specific natural antibodies. These data show that natural antibodies are a pool of relatively distinct immunoglobulins, and that antigen specificity may affect interpretation of natural antibody function and comparative immunology.
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Affiliation(s)
- Kendra Weston
- Department of Entomology, Washington State University, Pullman, WA, United States
| | | | - Jeb Owen
- Department of Entomology, Washington State University, Pullman, WA, United States
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9
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Meher AK, McNamara CA. B-1 lymphocytes in adipose tissue as innate modulators of inflammation linked to cardiometabolic disease. Immunol Rev 2024; 324:95-103. [PMID: 38747455 PMCID: PMC11262958 DOI: 10.1111/imr.13342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/23/2024]
Abstract
Fat is stored in distinct depots with unique features in both mice and humans and B cells reside in all adipose depots. We have shown that B cells modulate cardiometabolic disease through activities in two of these key adipose depots: visceral adipose tissue (VAT) and perivascular adipose tissue (PVAT). VAT refers to the adipose tissue surrounding organs, within the abdomen and thorax, and is comprised predominantly of white adipocytes. This depot has been implicated in mediating obesity-related dysmetabolism. PVAT refers to adipose tissue surrounding major arteries. It had long been thought to exist to provide protection and insulation for the vessel, yet recent work demonstrates an important role for PVAT in harboring immune cells, promoting their function and regulating the biology of the underlying vessel. The role of B-2 cells and adaptive immunity in adipose tissue biology has been nicely reviewed elsewhere. Given that, the predominance of B-1 cells in adipose tissue at homeostasis, and the emerging role of B-1 cells in a variety of disease states, we will focus this review on how B-1 cells function in VAT and PVAT depots to promote homeostasis and limit inflammation linked to cardiometabolic disease and factors that regulate this function.
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Affiliation(s)
- Akshaya K. Meher
- Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA
| | - Coleen A. McNamara
- Division of Cardiovascular Medicine, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA
- Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, USA
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10
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Alsina R, Riba M, Pérez-Millan A, Borrego-Écija S, Aldecoa I, Romera C, Balasa M, Antonell A, Lladó A, Compta Y, Del Valle J, Sánchez-Valle R, Pelegrí C, Molina-Porcel L, Vilaplana J. Increase in wasteosomes (corpora amylacea) in frontotemporal lobar degeneration with specific detection of tau, TDP-43 and FUS pathology. Acta Neuropathol Commun 2024; 12:97. [PMID: 38879502 PMCID: PMC11179228 DOI: 10.1186/s40478-024-01812-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 05/31/2024] [Indexed: 06/19/2024] Open
Abstract
Wasteosomes (or corpora amylacea) are polyglucosan bodies that appear in the human brain with aging and in some neurodegenerative diseases, and have been suggested to have a potential role in a nervous system cleaning mechanism. Despite previous studies in several neurodegenerative disorders, their status in frontotemporal lobar degeneration (FTLD) remains unexplored. Our study aims to characterize wasteosomes in the three primary FTLD proteinopathies, assessing frequency, distribution, protein detection, and association with aging or disease duration. Wasteosome scores were obtained in various brain regions from 124 post-mortem diagnosed sporadic FTLD patients, including 75 participants with tau (FTLD-tau), 42 with TAR DNA-binding protein 43 (FTLD-TDP), and 7 with Fused in Sarcoma (FTLD-FUS) proteinopathies, along with 29 control subjects. The wasteosome amount in each brain region for the different FLTD patients was assessed with a permutation test with age at death and sex as covariables, and multiple regressions explored associations with age at death and disease duration. Double immunofluorescence studies examined altered proteins linked to FTLD in wasteosomes. FTLD patients showed a higher accumulation of wasteosomes than control subjects, especially those with FTLD-FUS. Unlike FTLD-TDP and control subjects, wasteosome accumulation did not increase with age in FTLD-tau and FTLD-FUS. Cases with shorter disease duration in FTLD-tau and FTLD-FUS seemed to exhibit higher wasteosome quantities, whereas FTLD-TDP appeared to show an increase with disease progression. Immunofluorescence studies revealed the presence of tau and phosphorylated-TDP-43 in the periphery of isolated wasteosomes in some patients with FTLD-tau and FTLD-TDP, respectively. Central inclusions of FUS were observed in a higher number of wasteosomes in FTLD-FUS patients. These findings suggest a role of wasteosomes in FTLD, especially in the more aggressive forms of FLTD-FUS. Detecting these proteins, particularly FUS, in wasteosomes from cerebrospinal fluid could be a potential biomarker for FTLD.
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Affiliation(s)
- Raquel Alsina
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Avda. Joan XXIII 27-31, 08028, Barcelona, Spain
- Institut de Neurociències (UBNeuro), Universitat de Barcelona, Barcelona, Spain
- Centros de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | - Marta Riba
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Avda. Joan XXIII 27-31, 08028, Barcelona, Spain.
- Institut de Neurociències (UBNeuro), Universitat de Barcelona, Barcelona, Spain.
- Centros de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
| | - Agnès Pérez-Millan
- Institut de Neurociències (UBNeuro), Universitat de Barcelona, Barcelona, Spain
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Sergi Borrego-Écija
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Iban Aldecoa
- Neurological Tissue Bank of the Biobanc-Hospital Clínic-FRCB-IDIBAPS, Barcelona, Spain
- Department of Pathology, Biomedical Diagnostic Center (CBD), Hospital Clínic de Barcelona, FRCB-IDIBAPS, Universitat de Barcelona, Barcelona, Spain
| | - Clara Romera
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Avda. Joan XXIII 27-31, 08028, Barcelona, Spain
- Institut de Neurociències (UBNeuro), Universitat de Barcelona, Barcelona, Spain
- Centros de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | - Mircea Balasa
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Anna Antonell
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Albert Lladó
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Yaroslau Compta
- Institut de Neurociències (UBNeuro), Universitat de Barcelona, Barcelona, Spain
- Centros de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
- Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, FRCB-IDIBAPS, European Reference Network On Rare Neurological Diseases (ERN-RND), Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR), Barcelona, Spain
| | - Jaume Del Valle
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Avda. Joan XXIII 27-31, 08028, Barcelona, Spain
- Institut de Neurociències (UBNeuro), Universitat de Barcelona, Barcelona, Spain
- Centros de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | - Raquel Sánchez-Valle
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Carme Pelegrí
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Avda. Joan XXIII 27-31, 08028, Barcelona, Spain.
- Institut de Neurociències (UBNeuro), Universitat de Barcelona, Barcelona, Spain.
- Centros de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
| | - Laura Molina-Porcel
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Universitat de Barcelona, Barcelona, Spain
- Neurological Tissue Bank of the Biobanc-Hospital Clínic-FRCB-IDIBAPS, Barcelona, Spain
| | - Jordi Vilaplana
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Avda. Joan XXIII 27-31, 08028, Barcelona, Spain
- Institut de Neurociències (UBNeuro), Universitat de Barcelona, Barcelona, Spain
- Centros de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
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11
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Sarrigeorgiou I, Rouka E, Kotsiou OS, Perlepe G, Gerovasileiou ES, Gourgoulianis KI, Lymberi P, Zarogiannis SG. Natural antibodies targeting LPS in pleural effusions of various etiologies. Am J Physiol Lung Cell Mol Physiol 2024; 326:L727-L735. [PMID: 38591123 DOI: 10.1152/ajplung.00377.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 03/01/2024] [Accepted: 03/26/2024] [Indexed: 04/10/2024] Open
Abstract
Respiratory infection, cancer, and heart failure can cause abnormal accumulation of fluid in the pleural cavity. The immune responses within the cavity are orchestrated by leucocytes that reside in the serosal-associated lymphoid tissue. Natural antibodies (NAbs) are abundant in the serum (S) having a major role in systemic and mucosal immunity; however, their occurrence in pleural fluid (PF) remains an open question. Our aim herein was to detect and measure the levels of NAbs (IgM, IgG, IgA) targeting lipopolysaccharides (LPS) in both the pleural fluid and the serum of 78 patients with pleural effusions (PEs) of various etiologies. The values of anti-LPS NAb activity were extracted through a normalization step regarding the total IgM, IgG, and IgA levels, all determined by in-house ELISA. In addition, the ratios of PF/S values were analyzed further with other critical biochemical parameters from pleural fluids. Anti-LPS NAbs of all Ig classes were detected in most of the samples, while a significant increase of anti-LPS activity was observed in infectious and noninfectious compared with malignant PEs. Multivariate linear regression confirmed a negative correlation of IgM and IgA anti-LPS PF/S ratio with malignancy. Moreover, anti-LPS NAbs PF/S measurements led to increased positive and negative predictive power in ROC curves generated for the discrimination between benign and malignant PEs. Our results highlight the role of anti-LPS NAbs in the pleural cavity and demonstrate the potential translational impact that should be further explored.NEW & NOTEWORTHY Here we describe the detection and quantification of natural antibodies (NAbs) in the human pleural cavity. We show for the first time that IgM, IgG, and IgA anti-LPS natural antibodies are detected and measured in pleural effusions of infectious, noninfectious, and malignant etiologies and provide clinical correlates to demonstrate the translational impact of our findings.
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Affiliation(s)
- Ioannis Sarrigeorgiou
- Laboratory of Immunology, Department of Immunology, Hellenic Pasteur Institute, Athens, Greece
| | - Erasmia Rouka
- Department of Nursing, School of Health Sciences, University of Thessaly, Larissa, Greece
| | - Ourania S Kotsiou
- Department of Nursing, School of Health Sciences, University of Thessaly, Larissa, Greece
| | - Garyfallia Perlepe
- Department of Respiratory Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
| | - Efrosini S Gerovasileiou
- Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
| | - Konstantinos I Gourgoulianis
- Department of Respiratory Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
| | - Peggy Lymberi
- Laboratory of Immunology, Department of Immunology, Hellenic Pasteur Institute, Athens, Greece
| | - Sotirios G Zarogiannis
- Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
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12
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Berteselli GV, Filipe J, Martelli A, Vezzaro G, Canali E, Dall’Ara P. Salivary IgG and IgA in newborn calves and the possible role in the assessment of passive immunity transfer. Front Vet Sci 2024; 11:1383379. [PMID: 38863449 PMCID: PMC11166127 DOI: 10.3389/fvets.2024.1383379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 05/06/2024] [Indexed: 06/13/2024] Open
Abstract
Introduction The transfer of immunoglobulins from the mother to newborns is widely recognized as a critical event for safeguarding offspring against potentially life-threatening infectious diseases. Mainly for this reason, this study aimed to assess the concentrations of immunoglobulin G (IgG) and immunoglobulin A (IgA) in the saliva of newborn calves and explore its potential use for monitoring passive immunity transfer from cows to calves, as also to evaluate how colostrum intake affects serum and saliva IgG and IgA concentrations. Methods The quality of colostrum samples was evaluated using an optical refractometer before administration to the calves. Saliva and blood samples from 24 calves were obtained at the day of birth (T0) and 2 days after (T2) for determination of serum concentrations of total protein by refractometer, IgG and IgA (both on serum and saliva) by ELISA test. Results Positive correlations were observed between salivary IgA at T2 and salivary IgG at T2. A significant increase in both IgG and IgA levels in calf serum and saliva was noted. Salivary IgA levels can reflect salivary IgG levels. Discussion These findings suggest the potential utility of IgA in monitoring passive immunity transfer, and do not exclude saliva as an alternative, practical, and non-invasive matrix for assessing passive immunity transfer.
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Affiliation(s)
- G. V. Berteselli
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell’Università, Lodi, Italy
| | - J. Filipe
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell’Università, Lodi, Italy
| | - A. Martelli
- Fiamenghi Domenico, Gianluigi, Claudio e Matteo S.S. Cascina San Giacomo, Strada San Giacomo, San Bassano, Cremona, Italy
| | - G. Vezzaro
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell’Università, Lodi, Italy
| | - E. Canali
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell’Università, Lodi, Italy
| | - P. Dall’Ara
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Via dell’Università, Lodi, Italy
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13
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Uemoto Y, Katsura T, Endo Y, Tanaka K, Zhuang T, Urakawa M, Baba T, Yoshida G, Wang H, Kitazawa H, Shirakawa H, Nakamura T, Nochi T, Aso H. Genetic aspects of immunoglobulins and cyclophilin A in milk as potential indicators of mastitis resistance in Holstein cows. J Dairy Sci 2024; 107:1577-1591. [PMID: 37806629 DOI: 10.3168/jds.2022-23075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 09/18/2023] [Indexed: 10/10/2023]
Abstract
Mastitis is one of the most frequent and costly diseases affecting dairy cattle. Natural antibodies (immunoglobulins) and cyclophilin A (CyPA), the most abundant member of the family of peptidyl prolyl cis/trans isomerases, in milk may serve as indicators of mastitis resistance in dairy cattle. However, genetic information for CyPA is not available, and knowledge on the genetic and nongenetic relationships between these immune-related traits and somatic cell score (SCS) and milk yield in dairy cattle is sparse. Therefore, we aimed to comprehensively evaluate whether immune-related traits consisting of 5 Ig classes (IgG, IgG1, IgG2, IgA, and IgM) and CyPA in the test-day milk of Holstein cows can be used as genetic indicators of mastitis resistance by evaluating the genetic and nongenetic relationships with SCS in milk. The nongenetic factors affecting immune-related traits and the effects of these traits on SCS were evaluated. Furthermore, the genetic parameters of immune-related traits according to health status and genetic relationships under different SCS environments were estimated. All immune-related traits were significantly associated with SCS and directly proportional. Additionally, evaluation using a classification tree revealed that IgA, IgG2, and IgG were associated with SCS levels. Genetic factor analyses indicated that heritability estimates were low for CyPA (0.08) but moderate for IgG (0.37), IgA (0.44), and IgM (0.44), with positive genetic correlations among Ig (0.25-0.96). We also evaluated the differences in milk yield and SCS of cows between the low and high groups according to their sires' estimated breeding value for immune-related traits. In the high group, IgA had a significantly lower SCS in milk at 7 to 30 d compared with that in the low group. Furthermore, the Ig in milk had high positive genetic correlations between healthy and infected conditions (0.82-0.99), suggesting that Ig in milk under healthy conditions could interact with those under infected conditions, owing to the genetic ability based on the level of Ig in milk. Thus, Ig in milk are potential indicators for the genetic selection of mastitis resistance. However, because only the relationship between immune-related traits and SCS was investigated in this study, further study on the relationship between clinical mastitis and Ig in milk is needed before Ig can be used as an indicator of mastitis resistance.
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Affiliation(s)
- Yoshinobu Uemoto
- Animal Breeding and Genetics, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 980-8572, Japan.
| | - Teppei Katsura
- Animal Functional Morphology, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 980-8572, Japan
| | - Yuma Endo
- Animal Functional Morphology, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 980-8572, Japan
| | - Koutaro Tanaka
- Animal Functional Morphology, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 980-8572, Japan
| | - Tao Zhuang
- Laboratory of Animal Health Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 980-8572, Japan
| | - Megumi Urakawa
- Laboratory of Animal Health Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 980-8572, Japan
| | - Toshimi Baba
- Holstein Cattle Association of Japan, Hokkaido Branch, Sapporo, Hokkaido 001-8555, Japan
| | - Gaku Yoshida
- Shihoro Agricultural Cooperative, Kato District, Hokkaido 080-1219, Japan
| | - Haifei Wang
- Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
| | - Haruki Kitazawa
- Laboratory of Animal Health Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 980-8572, Japan; Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 980-8572, Japan
| | - Hitoshi Shirakawa
- Laboratory of Animal Health Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 980-8572, Japan; Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 980-8572, Japan
| | - Takehiko Nakamura
- Laboratory of Animal Health Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 980-8572, Japan
| | - Tomonori Nochi
- Animal Functional Morphology, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 980-8572, Japan; Laboratory of Animal Health Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 980-8572, Japan
| | - Hisashi Aso
- Laboratory of Animal Health Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 980-8572, Japan; The Cattle Museum, Oshu, Iwate 029-4205, Japan.
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14
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Happonen N, Härma MA, Akhi R, Nissinen AE, Savolainen MJ, Ruuth M, Öörni K, Adeshara K, Lehto M, Groop PH, Koivukangas V, Hukkanen J, Hörkkö S. Impact of RYGB surgery on plasma immunoglobulins: association between blood pressure and glucose levels six months after surgery. APMIS 2024; 132:187-197. [PMID: 38149431 DOI: 10.1111/apm.13366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 11/23/2023] [Indexed: 12/28/2023]
Abstract
We aimed to study levels of natural antibodies in plasma, and their associations to clinical and fecal biomarkers, before and 6 months after Roux-en-Y gastric bypass (RYGB) surgery. Thirty individuals with obesity [16 type 2 diabetic, 14 non-diabetic (ND)] had RYGB surgery. Total plasma IgA, IgG and IgM antibody levels and specific antibodies to oxidized low-density lipoprotein (oxLDL), malondialdehyde-acetaldehyde adducts, Porphyromonas gingivalis gingipain A hemagglutinin domain (Rgp44), and phosphocholine were measured using chemiluminescence immunoassay. Associations between plasma and fecal antibodies as well as clinical markers were analyzed. RYGB surgery reduced blood pressure, and the glycemic state was improved. A higher level of diastolic blood pressure was associated with lower plasma antibodies to oxLDL after surgery. Also, lower level of glucose markers associated with lower level of plasma antibodies to bacterial virulence factors. Antibodies to oxLDL decreased after surgery, and positive association between active serum lipopolysaccharide and specific oxLDL antibodies was detected. Total IgG levels decreased after surgery, but only in ND individuals. Reduced level of total plasma IgG, improved state of hypertension and hyperglycemia and their associations with decreased levels of specific antibodies in plasma, suggest an improved state of systemic inflammation after RYGB surgery.
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Affiliation(s)
- Natalie Happonen
- Medical Microbiology and Immunology, Research Unit of Biomedicine and Internal Medicine, University of Oulu, Oulu, Finland
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
- Nordlab, Oulu University Hospital, Oulu, Finland
| | - Mari-Anne Härma
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Ramin Akhi
- Medical Microbiology and Immunology, Research Unit of Biomedicine and Internal Medicine, University of Oulu, Oulu, Finland
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Antti E Nissinen
- Medical Microbiology and Immunology, Research Unit of Biomedicine and Internal Medicine, University of Oulu, Oulu, Finland
| | - Markku J Savolainen
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
- Research Unit of Biomedicine and Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
| | - Maija Ruuth
- Atherosclerosis Research Laboratory, Wihuri Research Institute, Helsinki, Finland
| | - Katariina Öörni
- Atherosclerosis Research Laboratory, Wihuri Research Institute, Helsinki, Finland
- Molecular and Integrative Biosciences, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland
| | - Krishna Adeshara
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Markku Lehto
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Per-Henrik Groop
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Vesa Koivukangas
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
- Department of Surgery, Oulu University Hospital, Oulu, Finland
| | - Janne Hukkanen
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
- Research Unit of Biomedicine and Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
| | - Sohvi Hörkkö
- Medical Microbiology and Immunology, Research Unit of Biomedicine and Internal Medicine, University of Oulu, Oulu, Finland
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
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15
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Simon D, Erdő-Bonyár S, Böröcz K, Balázs N, Badawy A, Bajnok A, Nörenberg J, Serény-Litvai T, Várnagy Á, Kovács K, Hantosi E, Mezősi E, Németh P, Berki T. Altered Levels of Natural Autoantibodies against Heat Shock Proteins in Pregnant Women with Hashimoto's Thyroiditis. Int J Mol Sci 2024; 25:1423. [PMID: 38338701 PMCID: PMC10855109 DOI: 10.3390/ijms25031423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 01/19/2024] [Accepted: 01/21/2024] [Indexed: 02/12/2024] Open
Abstract
The function of natural autoantibodies (nAAbs) in maintaining immunological tolerance has been comprehensively explained; however, their function in pregnant patients dealing with autoimmune diseases has not been thoroughly investigated. As Hashimoto's thyroiditis (HT) is the predominant organ-specific autoimmune condition of women of childbearing age, this study's objective was to evaluate IgM and IgG nAAbs targeting mitochondrial citrate synthase (CS) and heat shock proteins (Hsp60 and Hsp70) in women diagnosed with HT who were pregnant (HTP). Serum samples collected from HTP and healthy pregnant (HP) women in the first and third trimesters were tested using in-house-developed enzyme-linked immunosorbent assays (ELISAs). Our findings indicate the stability of nAAbs against CS and Hsps throughout the pregnancies of both healthy women and those with HT. However, during both trimesters, HTP patients displayed elevated levels of IgM isotype nAAbs against Hsp60 and Hsp70 compared to HP women, suggesting a regulatory role of IgM nAAbs during the pregnancies of patients with HT. Nonetheless, levels of IgG isotype nAAbs against Hsps were lower solely in the third trimester among HTP patients, resulting in a higher IgM/IgG ratio, which indicates their importance in alterations of the nAAb network during pregnancy in patients with HT.
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Affiliation(s)
- Diána Simon
- Department of Immunology and Biotechnology, Clinical Center, Medical School, University of Pécs, 7624 Pécs, Hungary
- National Laboratory on Human Reproduction, University of Pécs, 7624 Pécs, Hungary
| | - Szabina Erdő-Bonyár
- Department of Immunology and Biotechnology, Clinical Center, Medical School, University of Pécs, 7624 Pécs, Hungary
- National Laboratory on Human Reproduction, University of Pécs, 7624 Pécs, Hungary
| | - Katalin Böröcz
- Department of Immunology and Biotechnology, Clinical Center, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Noémi Balázs
- Department of Immunology and Biotechnology, Clinical Center, Medical School, University of Pécs, 7624 Pécs, Hungary
- National Laboratory on Human Reproduction, University of Pécs, 7624 Pécs, Hungary
| | - Ahmed Badawy
- Department of Immunology and Biotechnology, Clinical Center, Medical School, University of Pécs, 7624 Pécs, Hungary
- National Laboratory on Human Reproduction, University of Pécs, 7624 Pécs, Hungary
| | - Anna Bajnok
- National Laboratory on Human Reproduction, University of Pécs, 7624 Pécs, Hungary
- Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary
- Department of Obstetrics and Gynecology, Clinical Center, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Jasper Nörenberg
- National Laboratory on Human Reproduction, University of Pécs, 7624 Pécs, Hungary
- Department of Obstetrics and Gynecology, Clinical Center, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Tímea Serény-Litvai
- Department of Immunology and Biotechnology, Clinical Center, Medical School, University of Pécs, 7624 Pécs, Hungary
- National Laboratory on Human Reproduction, University of Pécs, 7624 Pécs, Hungary
- Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary
| | - Ákos Várnagy
- National Laboratory on Human Reproduction, University of Pécs, 7624 Pécs, Hungary
- Department of Obstetrics and Gynecology, Clinical Center, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Kálmán Kovács
- National Laboratory on Human Reproduction, University of Pécs, 7624 Pécs, Hungary
- Department of Obstetrics and Gynecology, Clinical Center, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Eszter Hantosi
- Department of Obstetrics and Gynecology, Clinical Center, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Emese Mezősi
- National Laboratory on Human Reproduction, University of Pécs, 7624 Pécs, Hungary
- First Department of Internal Medicine, Clinical Center, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Péter Németh
- Department of Immunology and Biotechnology, Clinical Center, Medical School, University of Pécs, 7624 Pécs, Hungary
- National Laboratory on Human Reproduction, University of Pécs, 7624 Pécs, Hungary
| | - Tímea Berki
- Department of Immunology and Biotechnology, Clinical Center, Medical School, University of Pécs, 7624 Pécs, Hungary
- National Laboratory on Human Reproduction, University of Pécs, 7624 Pécs, Hungary
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16
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Ling B, Ko JH, Stordy B, Zhang Y, Didden TF, Malounda D, Swift MB, Chan WCW, Shapiro MG. Gas Vesicle-Blood Interactions Enhance Ultrasound Imaging Contrast. NANO LETTERS 2023; 23:10748-10757. [PMID: 37983479 PMCID: PMC10722532 DOI: 10.1021/acs.nanolett.3c02780] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 11/10/2023] [Accepted: 11/13/2023] [Indexed: 11/22/2023]
Abstract
Gas vesicles (GVs) are genetically encoded, air-filled protein nanostructures of broad interest for biomedical research and clinical applications, acting as imaging and therapeutic agents for ultrasound, magnetic resonance, and optical techniques. However, the biomedical applications of GVs as systemically injectable nanomaterials have been hindered by a lack of understanding of GVs' interactions with blood components, which can significantly impact in vivo behavior. Here, we investigate the dynamics of GVs in the bloodstream using a combination of ultrasound and optical imaging, surface functionalization, flow cytometry, and mass spectrometry. We find that erythrocytes and serum proteins bind to GVs and shape their acoustic response, circulation time, and immunogenicity. We show that by modifying the GV surface we can alter these interactions and thereby modify GVs' in vivo performance. These results provide critical insights for the development of GVs as agents for nanomedicine.
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Affiliation(s)
- Bill Ling
- Division
of Chemistry and Chemical Engineering, California
Institute of Technology, Pasadena, California 91125, United States
| | - Jeong Hoon Ko
- Division
of Chemistry and Chemical Engineering, California
Institute of Technology, Pasadena, California 91125, United States
| | - Benjamin Stordy
- Institute
of Biomedical Engineering, University of
Toronto, Toronto, ON M5S 3G9, Canada
- Terrence
Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, Toronto, ON M5S
3E1, Canada
| | - Yuwei Zhang
- Institute
of Biomedical Engineering, University of
Toronto, Toronto, ON M5S 3G9, Canada
- Terrence
Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, Toronto, ON M5S
3E1, Canada
- Department
of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada
| | - Tighe F. Didden
- Division
of Chemistry and Chemical Engineering, California
Institute of Technology, Pasadena, California 91125, United States
| | - Dina Malounda
- Division
of Chemistry and Chemical Engineering, California
Institute of Technology, Pasadena, California 91125, United States
| | - Margaret B. Swift
- Division
of Chemistry and Chemical Engineering, California
Institute of Technology, Pasadena, California 91125, United States
| | - Warren C. W. Chan
- Institute
of Biomedical Engineering, University of
Toronto, Toronto, ON M5S 3G9, Canada
- Terrence
Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, Toronto, ON M5S
3E1, Canada
- Department
of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada
| | - Mikhail G. Shapiro
- Division
of Chemistry and Chemical Engineering, California
Institute of Technology, Pasadena, California 91125, United States
- Division
of Engineering and Applied Science, California
Institute of Technology, Pasadena, California 91125, United States
- Howard Hughes
Medical Institute, California Institute
of Technology, Pasadena, California 91125, United States
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17
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Ling B, Ko JH, Stordy B, Zhang Y, Didden TF, Malounda D, Swift MB, Chan WC, Shapiro MG. Gas vesicle-blood interactions enhance ultrasound imaging contrast. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.07.24.550434. [PMID: 37546852 PMCID: PMC10402017 DOI: 10.1101/2023.07.24.550434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/08/2023]
Abstract
Gas vesicles (GVs) are genetically encoded, air-filled protein nanostructures of broad interest for biomedical research and clinical applications, acting as imaging and therapeutic agents for ultrasound, magnetic resonance, and optical techniques. However, the biomedical applications of GVs as a systemically injectable nanomaterial have been hindered by a lack of understanding of GVs' interactions with blood components, which can significantly impact in vivo performance. Here, we investigate the dynamics of GVs in the bloodstream using a combination of ultrasound and optical imaging, surface functionalization, flow cytometry, and mass spectrometry. We find that erythrocytes and serum proteins bind to GVs and shape their acoustic response, circulation time, and immunogenicity. We show that by modifying the GV surface, we can alter these interactions and thereby modify GVs' in vivo performance. These results provide critical insights for the development of GVs as agents for nanomedicine.
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Affiliation(s)
- Bill Ling
- Division of Chemistry and Chemical Engineering, California Institute of Technology; Pasadena, CA 91125, USA
- These authors contributed equally to this work
| | - Jeong Hoon Ko
- Division of Chemistry and Chemical Engineering, California Institute of Technology; Pasadena, CA 91125, USA
- These authors contributed equally to this work
| | - Benjamin Stordy
- Institute of Biomedical Engineering, University of Toronto; Toronto, ON M5S 3G9, Canada
- Terence Donnelly Centre for Cellular & Biomolecular Research, University of Toronto; Toronto, ON M5S 3E1, Canada
| | - Yuwei Zhang
- Institute of Biomedical Engineering, University of Toronto; Toronto, ON M5S 3G9, Canada
- Terence Donnelly Centre for Cellular & Biomolecular Research, University of Toronto; Toronto, ON M5S 3E1, Canada
- Department of Chemistry, University of Toronto; Toronto, ON M5S 3H6, Canada
| | - Tighe F. Didden
- Division of Chemistry and Chemical Engineering, California Institute of Technology; Pasadena, CA 91125, USA
| | - Dina Malounda
- Division of Chemistry and Chemical Engineering, California Institute of Technology; Pasadena, CA 91125, USA
| | - Margaret B. Swift
- Division of Chemistry and Chemical Engineering, California Institute of Technology; Pasadena, CA 91125, USA
| | - Warren C.W. Chan
- Institute of Biomedical Engineering, University of Toronto; Toronto, ON M5S 3G9, Canada
- Terence Donnelly Centre for Cellular & Biomolecular Research, University of Toronto; Toronto, ON M5S 3E1, Canada
- Department of Chemistry, University of Toronto; Toronto, ON M5S 3H6, Canada
| | - Mikhail G. Shapiro
- Division of Chemistry and Chemical Engineering, California Institute of Technology; Pasadena, CA 91125, USA
- Division of Engineering and Applied Science, California Institute of Technology; Pasadena, CA 91125, USA
- Howard Hughes Medical Institute; Pasadena, CA 91125, USA
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18
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Ebrahimian T, Dierick F, Ta V, Kotsiopriftis M, O'Connor Miranda J, Mann KK, Orthwein A, Lehoux S. B cell-specific knockout of AID protects against atherosclerosis. Sci Rep 2023; 13:8723. [PMID: 37253865 DOI: 10.1038/s41598-023-35980-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 05/26/2023] [Indexed: 06/01/2023] Open
Abstract
Antigen-naive IgM-producing B cells are atheroprotective, whereas mature B cells producing class-switched antibodies promote atherosclerosis. Activation-induced cytidine deaminase (AID), which mediates class switch recombination (CSR), would thus be expected to foster atherosclerosis. Yet, AID also plays a major role in the establishment of B cell tolerance. We sought to define whether AID affects atherosclerotic plaque formation. We generated Ldlr-/- chimeras transplanted with bone marrow from Aicda-/- or wild-type (WT) mice, fed a HFD for 14 weeks. Decreased B cell maturation in Ldlr-/-Aicda-/- mice was demonstrated by 50% reduction in splenic and aortic BAFFR expression, a key signaling component of B2 cell maturation. This was associated with increased plasma IgM in Ldlr-/-Aicda-/- compared with Ldlr-/-WT animals. Importantly, Ldlr-/-Aicda-/- mice had reduced atherosclerotic lesion area (0.20 ± 0.03mm2) compared with Ldlr-/-WT (0.30 ± 0.04mm2, P < 0.05), although no differences in plaque composition were noted between groups. In addition, immunofluorescence analysis revealed increased splenic B and T cell areas independent of cell number. AID depletion directly inhibits atherosclerotic plaque formation.
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Affiliation(s)
- Talin Ebrahimian
- Lady Davis Institute for Medical Research, 3755, Cote Ste Catherine, Montreal, QC, H3T 1E2, Canada.
| | - France Dierick
- Lady Davis Institute for Medical Research, 3755, Cote Ste Catherine, Montreal, QC, H3T 1E2, Canada
| | - Vincent Ta
- Lady Davis Institute for Medical Research, 3755, Cote Ste Catherine, Montreal, QC, H3T 1E2, Canada
| | - Maria Kotsiopriftis
- Lady Davis Institute for Medical Research, 3755, Cote Ste Catherine, Montreal, QC, H3T 1E2, Canada
| | | | - Koren K Mann
- Lady Davis Institute for Medical Research, 3755, Cote Ste Catherine, Montreal, QC, H3T 1E2, Canada
| | - Alexandre Orthwein
- Lady Davis Institute for Medical Research, 3755, Cote Ste Catherine, Montreal, QC, H3T 1E2, Canada
| | - Stephanie Lehoux
- Lady Davis Institute for Medical Research, 3755, Cote Ste Catherine, Montreal, QC, H3T 1E2, Canada.
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19
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Hiéronimus L, Huaux F. B-1 cells in immunotoxicology: Mechanisms underlying their response to chemicals and particles. FRONTIERS IN TOXICOLOGY 2023; 5:960861. [PMID: 37143777 PMCID: PMC10151831 DOI: 10.3389/ftox.2023.960861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 03/31/2023] [Indexed: 05/06/2023] Open
Abstract
Since their discovery nearly 40 years ago, B-1 cells have continued to challenge the boundaries between innate and adaptive immunity, as well as myeloid and lymphoid functions. This B-cell subset ensures early immunity in neonates before the development of conventional B (B-2) cells and respond to immune injuries throughout life. B-1 cells are multifaceted and serve as natural- and induced-antibody-producing cells, phagocytic cells, antigen-presenting cells, and anti-/pro-inflammatory cytokine-releasing cells. This review retraces the origin of B-1 cells and their different roles in homeostatic and infectious conditions before focusing on pollutants comprising contact-sensitivity-inducing chemicals, endocrine disruptors, aryl hydrocarbon receptor (AHR) ligands, and reactive particles.
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20
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Han B, van den Berg H, Loonen MJ, Mateo R, van den Brink NW. Mercury-Modulated Immune Responses in Arctic Barnacle Goslings ( Branta leucopsis) upon a Viral-Like Immune Challenge. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2023; 57:5337-5348. [PMID: 36940419 PMCID: PMC10077589 DOI: 10.1021/acs.est.2c07622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 03/10/2023] [Accepted: 03/10/2023] [Indexed: 06/18/2023]
Abstract
Historical mining activities in Svalbard (79°N/12°E) have caused local mercury (Hg) contamination. To address the potential immunomodulatory effects of environmental Hg on Arctic organisms, we collected newborn barnacle goslings (Branta leucopsis) and herded them in either a control or mining site, differing in Hg levels. An additional group at the mining site was exposed to extra inorganic Hg(II) via supplementary feed. Hepatic total Hg concentrations differed significantly between the control (0.011 ± 0.002 mg/kg dw), mine (0.043 ± 0.011 mg/kg dw), and supplementary feed (0.713 ± 0.137 mg/kg dw) gosling groups (average ± standard deviation). Upon immune challenge with double-stranded RNA (dsRNA) injection, endpoints for immune responses and oxidative stress were measured after 24 h. Our results indicated that Hg exposure modulated the immune responses in Arctic barnacle goslings upon a viral-like immune challenge. Increased exposure to both environmental as well as supplemental Hg reduced the level of natural antibodies, suggesting impaired humoral immunity. Hg exposure upregulated the expression of proinflammatory genes in the spleen, including inducible nitric oxide synthase (iNOS) and interleukin 18 (IL18), suggesting Hg-induced inflammatory effects. Exposure to Hg also oxidized glutathione (GSH) to glutathione disulfide (GSSG); however, goslings were capable of maintaining the redox balance by de novo synthesis of GSH. These adverse effects on the immune responses indicated that even exposure to low, environmentally relevant levels of Hg might affect immune competence at the individual level and might even increase the susceptibility of the population to infections.
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Affiliation(s)
- Biyao Han
- Wageningen
University, Division of Toxicology, Postal code 8000, NL-6700 EA Wageningen, The Netherlands
| | - Hans van den Berg
- Wageningen
University, Division of Toxicology, Postal code 8000, NL-6700 EA Wageningen, The Netherlands
| | - Maarten J.J.E. Loonen
- University
of Groningen, Arctic Centre, Aweg 30, NL-9718 CW Groningen, The Netherlands
| | - Rafael Mateo
- Instituto
de Investigación en Recursos Cinegéticos (IREC), Ronda de Toledo, 12, 13071 Ciudad Real, Spain
| | - Nico W. van den Brink
- Wageningen
University, Division of Toxicology, Postal code 8000, NL-6700 EA Wageningen, The Netherlands
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21
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Riba M, del Valle J, Romera C, Alsina R, Molina-Porcel L, Pelegrí C, Vilaplana J. Uncovering tau in wasteosomes (corpora amylacea) of Alzheimer’s disease patients. Front Aging Neurosci 2023; 15:1110425. [PMID: 37065464 PMCID: PMC10101234 DOI: 10.3389/fnagi.2023.1110425] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 03/14/2023] [Indexed: 04/01/2023] Open
Abstract
Brain corpora amylacea, recently renamed as wasteosomes, are polyglucosan bodies that appear during aging and some neurodegenerative conditions. They collect waste substances and are part of a brain cleaning mechanism. For decades, studies on their composition have produced inconsistent results and the presence of tau protein in them has been controversial. In this work, we reanalyzed the presence of this protein in wasteosomes and we pointed out a methodological problem when immunolabeling. It is well known that to detect tau it is necessary to perform an antigen retrieval. However, in the case of wasteosomes, an excessive antigen retrieval with boiling dissolves their polyglucosan structure, releases the entrapped proteins and, thus, prevents their detection. After performing an adequate pre-treatment, with an intermediate time of boiling, we observed that some brain wasteosomes from patients with Alzheimer’s disease (AD) contained tau, while we did not detect tau protein in those from non-AD patients. These observations pointed the different composition of wasteosomes depending on the neuropathological condition and reinforce the role of wasteosomes as waste containers.
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Affiliation(s)
- Marta Riba
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, Barcelona, Spain
- Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | - Jaume del Valle
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, Barcelona, Spain
- Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | - Clara Romera
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, Barcelona, Spain
- Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
| | - Raquel Alsina
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, Barcelona, Spain
- Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
| | - Laura Molina-Porcel
- Alzheimer’s Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clinic, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain
- Neurological Tissue Bank of the Biobanc-Hospital Clinic-IDIBAPS, Barcelona, Spain
| | - Carme Pelegrí
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, Barcelona, Spain
- Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
- *Correspondence: Carme Pelegrí,
| | - Jordi Vilaplana
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, Barcelona, Spain
- Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
- Jordi Vilaplana,
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22
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Lake BPM, Wylie RG, Bařinka C, Rullo AF. Tunable Multivalent Platform for Immune Recruitment to Lower Antigen Expressing Cancers. Angew Chem Int Ed Engl 2023; 62:e202214659. [PMID: 36577087 DOI: 10.1002/anie.202214659] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 12/12/2022] [Accepted: 12/28/2022] [Indexed: 12/30/2022]
Abstract
Chemical immunotherapeutic strategies including Antibody Recruiting Molecules (ARMs - bivalent small molecules containing an antibody-binding domain (ABD) and a target-binding domain (TBD)) direct immune-mediated clearance of diseased cells. Anti-cancer ARM function relies on high tumor antigen valency, limiting function against lower antigen expressing tumors. To address this limitation, we report a tunable multivalent immune recruitment (MIR) platform to amplify/stabilize antibody recruitment to cells with lower antigen valencies. An initial set of polymeric ARMs (pARMs) were synthesized and screened to evaluate ABD/TBD copy number, ratio, and steric occlusion on specific immune induction. Most pARMs demonstrated simultaneous high avidity binding to anti-dinitrophenyl antibodies and prostate-specific membrane antigens on prostate cancer. Optimized pARMs mediated enhanced anti-cancer immune function against lower antigen expressing target cells compared to an analogous ARM.
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Affiliation(s)
- Benjamin P M Lake
- Department of Medicine, Center for Discovery in Cancer Research, McMaster University, Hamilton, Ontario, L8S 4K1, Canada.,Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, L8S 4L8, Canada
| | - Ryan G Wylie
- Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, L8S 4L8, Canada.,School of Biomedical Engineering, McMaster University, Hamilton, Ontario, L8S 4M1, Canada
| | - Cyril Bařinka
- Institute of Biotechnology of the Czech Academy of Sciences, Průmyslová 595, 25250, Vestec, Czech Republic
| | - Anthony F Rullo
- Department of Medicine, Center for Discovery in Cancer Research, McMaster University, Hamilton, Ontario, L8S 4K1, Canada.,Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, L8S 4L8, Canada
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23
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Sarrigeorgiou I, Stivarou T, Tsinti G, Patsias A, Fotou E, Moulasioti V, Kyriakou D, Tellis C, Papadami M, Moussis V, Tsiouris V, Tsikaris V, Tsoukatos D, Lymberi P. Levels of Circulating IgM and IgY Natural Antibodies in Broiler Chicks: Association with Genotype and Farming Systems. BIOLOGY 2023; 12:biology12020304. [PMID: 36829580 PMCID: PMC9952908 DOI: 10.3390/biology12020304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 02/03/2023] [Accepted: 02/10/2023] [Indexed: 02/17/2023]
Abstract
Naturally occurring antibodies (NAbs), which are major components of innate immunity, exist in circulation under healthy conditions without prior antigenic stimulation and are able to recognize both self- and non-self-constituents. The present study aimed at identifying potential immunological differences between commercial fast- and slow-growth broilers (n = 555) raised in conventional and free-range systems, respectively, through the use of the specificity, isotypes and levels of circulating NAbs. The possible beneficial effect of oregano-based dietary supplementation was also evaluated. To this end, serum IgM and IgY NAbs against self- (actin and DNA) and non-self- antigens (trinitrophenol and lipopolysaccharide) were measured by ELISA and further correlated with genotype, season and performance. Significantly higher levels of IgM NAbs against all antigens were found in slow-growth compared to fast-growth broilers. IgM NAb levels were also significantly increased in dietarily supplemented slow-growth broilers versus those consuming standard feed. Moreover, significantly elevated levels of anti-DNA IgY NAbs were found in fast-growth compared to slow-growth broilers, whereas the opposite was observed for anti-LPS IgY NAbs. Multivariate linear regression analysis confirmed multiple interactions between NAb levels, genotype, season and performance. Overall, serum NAbs have proven to be valuable innovative immunotools in the poultry industry, efficiently differentiating fast-growing versus slow-growing broilers, and dietary supplementation of plant extracts can enhance natural immunity.
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Affiliation(s)
- Ioannis Sarrigeorgiou
- Immunology Laboratory, Immunology Department, Hellenic Pasteur Institute (HPI), 127, Vasilissis Sofias Avenue, 11521 Athens, Greece
| | - Theodora Stivarou
- Immunology Laboratory, Immunology Department, Hellenic Pasteur Institute (HPI), 127, Vasilissis Sofias Avenue, 11521 Athens, Greece
| | - Gerasimina Tsinti
- Immunology Laboratory, Immunology Department, Hellenic Pasteur Institute (HPI), 127, Vasilissis Sofias Avenue, 11521 Athens, Greece
| | - Apostolos Patsias
- Microbiology and Chemical Laboratory, Pindos APSI, 45500 Rodotopi Ioannina, Greece
| | - Evgenia Fotou
- Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioannina, Greece
| | - Vasiliki Moulasioti
- Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioannina, Greece
| | - Dimitra Kyriakou
- Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioannina, Greece
| | - Constantinos Tellis
- Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioannina, Greece
| | - Maria Papadami
- Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioannina, Greece
| | - Vassilios Moussis
- Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioannina, Greece
| | - Vasileios Tsiouris
- Microbiology and Chemical Laboratory, Pindos APSI, 45500 Rodotopi Ioannina, Greece
- Unit of Avian Medicine, Faculty of Veterinary Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Vassilios Tsikaris
- Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioannina, Greece
| | - Demokritos Tsoukatos
- Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioannina, Greece
| | - Peggy Lymberi
- Immunology Laboratory, Immunology Department, Hellenic Pasteur Institute (HPI), 127, Vasilissis Sofias Avenue, 11521 Athens, Greece
- Correspondence:
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24
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Oleinika K, Slisere B, Catalán D, Rosser EC. B cell contribution to immunometabolic dysfunction and impaired immune responses in obesity. Clin Exp Immunol 2022; 210:263-272. [PMID: 35960996 PMCID: PMC9384752 DOI: 10.1093/cei/uxac079] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 07/15/2022] [Accepted: 08/09/2022] [Indexed: 11/14/2022] Open
Abstract
Obesity increases the risk of type 2 diabetes mellitus, cardiovascular disease, fatty liver disease, and cancer. It is also linked with more severe complications from infections, including COVID-19, and poor vaccine responses. Chronic, low-grade inflammation and associated immune perturbations play an important role in determining morbidity in people living with obesity. The contribution of B cells to immune dysregulation and meta-inflammation associated with obesity has been documented by studies over the past decade. With a focus on human studies, here we consolidate the observations demonstrating that there is altered B cell subset composition, differentiation, and function both systemically and in the adipose tissue of individuals living with obesity. Finally, we discuss the potential factors that drive B cell dysfunction in obesity and propose a model by which altered B cell subset composition in obesity underlies dysfunctional B cell responses to novel pathogens.
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Affiliation(s)
- Kristine Oleinika
- Correspondence: Kristine Oleinika, Department of Internal Diseases, Riga Stradins University, Riga, Latvia.
| | - Baiba Slisere
- Department of Doctoral Studies, Riga Stradins University, Riga, Latvia
- Joint Laboratory, Pauls Stradins Clinical University Hospital, Riga, Latvia
| | - Diego Catalán
- Programa Disciplinario de Inmunología, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Elizabeth C Rosser
- Centre for Adolescent Rheumatology Versus Arthritis at UCL, UCLH and GOSH and Department of Rheumatology, Division of Medicine, University College London, London, UK
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25
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Slama SL, Williams GS, Painter MN, Sheedy MD, Sandmeier FC. Temperature and Season Influence Phagocytosis by B1 Lymphocytes in the Mojave Desert Tortoise. Integr Comp Biol 2022; 62:1683-1692. [PMID: 35536570 DOI: 10.1093/icb/icac025] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 04/08/2022] [Accepted: 04/11/2022] [Indexed: 01/05/2023] Open
Abstract
Lymphocytes are usually interpreted as functioning in adaptive immunity despite evidence that large proportions of these cells (B1 lymphocytes) have innate immune functions, including phagocytosis, in the peripheral blood of ectothermic vertebrates. We used a recently optimized assay to assess environmental influences on phagocytic activity of lymphocytes isolated from the Mojave desert tortoise (Gopherus agassizii). Previous studies suggest that lymphocytes in this species are associated with reduced pathogen loads, especially in cooler climates, and that lymphocyte numbers fluctuate seasonally. Thus, we evaluated thermal dependence of phagocytic activity in vitro and across seasons. While B1 lymphocytes appeared to be cold-adapted and always increased phagocytosis at cool temperatures, we also found evidence of thermal acclimation. Tortoises upregulated these lymphocytes during cooler seasons in the fall as their preferred body temperatures dropped, and phagocytosis also increased in efficiency during this same time. Like many other ectothermic species, populations of desert tortoises are in decline, in part due to a cold-adapted pathogen that causes chronic respiratory disease. Future studies, similarly focused on the function of B1 lymphocytes, could serve to uncover new patterns in thermal acclimation of immune functions and disease ecology across taxa of ectothermic vertebrates.
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Affiliation(s)
- Summer L Slama
- Department of Biology, Colorado State University-Pueblo, 2200 Bonforte Blvd Pueblo, CO 81001, USA
| | - Grace S Williams
- Department of Biology, Colorado State University-Pueblo, 2200 Bonforte Blvd Pueblo, CO 81001, USA
| | - Mariah N Painter
- Department of Biology, Colorado State University-Pueblo, 2200 Bonforte Blvd Pueblo, CO 81001, USA
| | - Maxwell D Sheedy
- Department of Biology, Colorado State University-Pueblo, 2200 Bonforte Blvd Pueblo, CO 81001, USA
| | - Franziska C Sandmeier
- Department of Biology, Colorado State University-Pueblo, 2200 Bonforte Blvd Pueblo, CO 81001, USA
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26
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Istomin N, Härma MA, Akhi R, Nissinen AE, Savolainen MJ, Adeshara K, Lehto M, Groop PH, Koivukangas V, Hukkanen J, Hörkkö S. Total fecal IgA levels increase and natural IgM antibodies decrease after gastric bypass surgery. APMIS 2022; 130:637-646. [PMID: 35959517 PMCID: PMC9805076 DOI: 10.1111/apm.13268] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 08/09/2022] [Indexed: 01/10/2023]
Abstract
Obesity is associated with low-grade inflammation and increased systemic oxidative stress. Roux-en-Y gastric bypass (RYGB) surgery is known to ameliorate the obesity-induced metabolic dysfunctions. We aimed to study the levels of natural antibodies in feces, before and 6 months after RYGB surgery in obese individuals with and without type 2 diabetes (T2D). Sixteen individuals with T2D and 14 non-diabetic (ND) individuals were operated. Total IgA, IgG and IgM antibody levels and specific antibodies to oxidized low-density lipoprotein (oxLDL), malondialdehyde-acetaldehyde adducts (MAA adducts), Porphyromonas gingivalis gingipain A hemagglutinin domain (Rgp44) and phosphocholine (PCho) were measured using chemiluminescence immunoassay. Total fecal IgA was elevated, while total IgM and IgG were not affected by the surgery. Fecal natural IgM specific to oxLDL decreased significantly in both T2D and ND individuals, while fecal IgM to Rgp44 and PCho decreased significantly in T2D individuals. A decrease in IgG to MAA-LDL, Rgp44 and PCho was detected. RYGB surgery increases the levels of total fecal IgA and decreases fecal natural IgG and IgM antibodies specific to oxLDL. Natural antibodies and IgA are important in maintaining the normal gut homeostasis and first-line defense against microbes, and their production is markedly altered with RYGB surgery.
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Affiliation(s)
- Natalie Istomin
- Medical Microbiology and Immunology, Research Unit of Biomedicine, University of Oulu, Oulu, Finland.,Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.,Nordlab, Oulu University Hospital, Oulu, Finland
| | - Mari-Anne Härma
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Clinical and Molecular Metabolism, Faculty of Medicine Research Programs, University of Helsinki, Helsinki, Finland
| | - Ramin Akhi
- Medical Microbiology and Immunology, Research Unit of Biomedicine, University of Oulu, Oulu, Finland.,Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Antti E Nissinen
- Medical Microbiology and Immunology, Research Unit of Biomedicine, University of Oulu, Oulu, Finland
| | - Markku J Savolainen
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.,Research Unit of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
| | - Krishna Adeshara
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Clinical and Molecular Metabolism, Faculty of Medicine Research Programs, University of Helsinki, Helsinki, Finland
| | - Markku Lehto
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Clinical and Molecular Metabolism, Faculty of Medicine Research Programs, University of Helsinki, Helsinki, Finland
| | - Per-Henrik Groop
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Clinical and Molecular Metabolism, Faculty of Medicine Research Programs, University of Helsinki, Helsinki, Finland
| | - Vesa Koivukangas
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.,Department of Surgery, Oulu University Hospital, Oulu, Finland
| | - Janne Hukkanen
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.,Research Unit of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
| | - Sohvi Hörkkö
- Medical Microbiology and Immunology, Research Unit of Biomedicine, University of Oulu, Oulu, Finland.,Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
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27
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Shenoy AT, De Ana CL, Barker KA, Arafa EI, Martin IM, Mizgerd JP, Belkina AC. CPHEN-011: Comprehensive phenotyping of murine lung resident lymphocytes after recovery from pneumococcal pneumonia. Cytometry A 2022; 101:892-902. [PMID: 34854229 PMCID: PMC9160214 DOI: 10.1002/cyto.a.24522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 11/15/2021] [Accepted: 11/17/2021] [Indexed: 01/27/2023]
Abstract
Recovery from pneumococcal (Spn) pneumonia induces development of tissue resident memory CD4+ TRM cells, BRM cells, and antibody secreting plasma cells in experienced lungs. These tissue resident lymphocytes confer protection against subsequent lethal challenge by serotype mismatched Spn (termed as heterotypic immunity). While traditional flow cytometry and gating strategies support premeditated identification of cells using a limited set of markers, discovery of novel tissue resident lymphocytes necessitates stable platforms that can handle larger sets of phenotypic markers and lends itself to unbiased clustering approaches. In this report, we leverage the power of full spectrum flow cytometry (FSFC) to develop a comprehensive panel of phenotypic markers that allows identification of multiple subsets of tissue resident lymphocytes in Spn-experienced murine lungs. Using Phenograph algorithm on this multidimensional data, we identify unforeseen heterogeneity in lung resident adaptive immune landscape which includes unexpected subsets of TRM and BRM cells. Further, using conventional gating strategy informed by our unsupervised clustering data, we confirm their presence exquisitely in Spn-experienced lungs as potentially relevant to heterotypic immunity and define CD73 as a highly expressed marker on TRM cells. Thus, our study emphasizes the utility of FSFC for confirmatory and discovery studies relating to tissue resident adaptive immunity.
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Affiliation(s)
- Anukul T. Shenoy
- Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA
| | - Carolina Lyon De Ana
- Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA
- Dept. of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA
| | - Kimberly A. Barker
- Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA
- Dept. of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA
| | - Emad I. Arafa
- Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA
- Dept. of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
| | - Ian M.C. Martin
- Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA
| | - Joseph P. Mizgerd
- Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA
- Dept. of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA
- Dept. of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
- Dept. of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA
| | - Anna C. Belkina
- Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA
- Flow Cytometry Core Facility, Boston University School of Medicine, Boston, MA, 02118, USA
- Dept. of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA
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Riba M, Campo-Sabariz J, Tena I, Molina-Porcel L, Ximelis T, Calvo M, Ferrer R, Martín-Venegas R, del Valle J, Vilaplana J, Pelegrí C. Wasteosomes (corpora amylacea) of human brain can be phagocytosed and digested by macrophages. Cell Biosci 2022; 12:177. [PMID: 36307854 PMCID: PMC9617366 DOI: 10.1186/s13578-022-00915-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 10/15/2022] [Indexed: 11/07/2022] Open
Abstract
Background Corpora amylacea of human brain, recently renamed as wasteosomes, are granular structures that appear during aging and also accumulate in specific areas of the brain in neurodegenerative conditions. Acting as waste containers, wasteosomes are formed by polyglucosan aggregates that entrap and isolate toxic and waste substances of different origins. They are expelled from the brain to the cerebrospinal fluid (CSF), and can be phagocytosed by macrophages. In the present study, we analyze the phagocytosis of wasteosomes and the mechanisms involved in this process. Accordingly, we purified wasteosomes from post-mortem extracted human CSF and incubated them with THP-1 macrophages. Immunofluorescence staining and time-lapse recording techniques were performed to evaluate the phagocytosis. We also immunostained human hippocampal sections to study possible interactions between wasteosomes and macrophages at central nervous system interfaces. Results We observed that the wasteosomes obtained from post-mortem extracted CSF are opsonized by MBL and the C3b complement protein. Moreover, we observed that CD206 and CD35 receptors may be involved in the phagocytosis of these wasteosomes by THP-1 macrophages. Once phagocytosed, wasteosomes become degraded and some of the resulting fractions can be exposed on the surface of macrophages and interchanged between different macrophages. However, brain tissue studies show that, in physiological conditions, CD206 but not CD35 receptors may be involved in the phagocytosis of wasteosomes. Conclusions The present study indicates that macrophages have the machinery required to process and degrade wasteosomes, and that macrophages can interact in different ways with wasteosomes. In physiological conditions, the main mechanism involve CD206 receptors and M2 macrophages, which trigger the phagocytosis of wasteosomes without inducing inflammatory responses, thus avoiding tissue damage. However, altered wasteosomes like those obtained from post-mortem extracted CSF, which may exhibit waste elements, become opsonized by MBL and C3b, and so CD35 receptors constitute another possible mechanism of phagocytosis, leading in this case to inflammatory responses. Supplementary Information The online version contains supplementary material available at 10.1186/s13578-022-00915-2.
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Affiliation(s)
- Marta Riba
- grid.5841.80000 0004 1937 0247Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain ,grid.5841.80000 0004 1937 0247Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain ,grid.418264.d0000 0004 1762 4012Centros de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | - Joan Campo-Sabariz
- grid.5841.80000 0004 1937 0247Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain ,grid.5841.80000 0004 1937 0247Institut de Recerca en Nutrició i Seguretat Alimentàries (INSA-UB), Universitat de Barcelona, Barcelona, Spain
| | - Iraida Tena
- grid.5841.80000 0004 1937 0247Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain
| | - Laura Molina-Porcel
- grid.410458.c0000 0000 9635 9413Alzheimer’s Disease and Other Cognitive Disorders Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Neurology Service, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain ,grid.10403.360000000091771775Neurological Tissue Bank of the Biobanc-Hospital Clinic-IDIBAPS, Barcelona, Spain
| | - Teresa Ximelis
- grid.410458.c0000 0000 9635 9413Alzheimer’s Disease and Other Cognitive Disorders Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Neurology Service, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain ,grid.10403.360000000091771775Neurological Tissue Bank of the Biobanc-Hospital Clinic-IDIBAPS, Barcelona, Spain
| | - Maria Calvo
- grid.5841.80000 0004 1937 0247Unitat de Microscòpia Òptica Avançada - Campus Clínic, Facultat de Medicina, Centres Científics i Tecnològics - Universitat de Barcelona, Barcelona, Spain
| | - Ruth Ferrer
- grid.5841.80000 0004 1937 0247Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain ,grid.5841.80000 0004 1937 0247Institut de Recerca en Nutrició i Seguretat Alimentàries (INSA-UB), Universitat de Barcelona, Barcelona, Spain
| | - Raquel Martín-Venegas
- grid.5841.80000 0004 1937 0247Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain ,grid.5841.80000 0004 1937 0247Institut de Recerca en Nutrició i Seguretat Alimentàries (INSA-UB), Universitat de Barcelona, Barcelona, Spain
| | - Jaume del Valle
- grid.5841.80000 0004 1937 0247Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain ,grid.5841.80000 0004 1937 0247Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain ,grid.418264.d0000 0004 1762 4012Centros de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | - Jordi Vilaplana
- grid.5841.80000 0004 1937 0247Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain ,grid.5841.80000 0004 1937 0247Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain ,grid.418264.d0000 0004 1762 4012Centros de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | - Carme Pelegrí
- grid.5841.80000 0004 1937 0247Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain ,grid.5841.80000 0004 1937 0247Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain ,grid.418264.d0000 0004 1762 4012Centros de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
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Vidal AS, de Campos Reis NF, De Lorenzo BHP, Alvares-Saraiva AM, Xander P, Novaes E Brito RR. Impact of sleep restriction in B-1 cells activation and differentiation. Immunobiology 2022; 227:152280. [PMID: 36179431 DOI: 10.1016/j.imbio.2022.152280] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 08/29/2022] [Accepted: 09/13/2022] [Indexed: 12/01/2022]
Abstract
B-1 lymphocytes are a subtype of B cells with functional and phenotypic features that differ from conventional B lymphocytes. These cells are mainly located in mice's pleural and peritoneal cavities and express unconventional B cell surface markers. B-1 cells participate in immunity by producing antibodies, cytokines, and chemokines and physically interacting with other immune cells. In addition, B-1 cells can differentiate into mononuclear phagocyte-like cells and phagocytize several pathogens. However, the activation and differentiation of B-1 cells are not entirely understood. It is known that several factors can influence B-1 cells, such as pathogens components and the immune response. This work aimed to evaluate the influence of chronic stress on B-1 cell activation and differentiation into phagocytes. The experimental sleep restriction was used as a stress model since the sleep alteration alters several immune cells' functions. Thus, mice were submitted to sleep restriction for 21 consecutive days, and the activation and differentiation of B-1 cells were analyzed. Our results demonstrated that B-1 cells initiated the differentiation process into mononuclear phagocytes after the period of sleep restriction. In addition, we detected a significant decrease in lymphoid lineage commitment factors (EBF, E2A, Blnk) (*P < 0.05) and an increase in the G-CSFR gene (related to the myeloid lineage commitment factor) (****P < 0.0001), as compared to control mice no submitted to sleep restriction. An increase in the co-stimulatory molecules CD80 and CD86 (**P < 0.01 and *P < 0.05, respectively) and a higher production of nitric oxide (NO) (*P < 0.05) and reactive oxygen species (ROS) (*P < 0.05) were also observed in B-1 cells from mice submitted to sleep restriction. Nevertheless, B-1 cells from sleep-restricted mice showed a significant reduction in the Toll-like receptors (TLR)-2, -6, and -9, and interleukine-10 (IL-10) cytokine expression (***P < 0.001) as compared to control. Sleep-restricted mice intraperitoneally infected withL. amazonensispromastigotes showed a reduction in the average internalized parasites (*P < 0.05) by B-1 cells. These findings suggest that sleep restriction interferes with B-1 lymphocyte activation and differentiation. In addition, b-1 cells assumed a more myeloid profile but with a lower phagocytic capacity in this stress condition.
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Affiliation(s)
- Andrey Sladkevicius Vidal
- Centro Universitário São Camilo, Centro Universitário São Camilo, Av. Nazaré, 1501, São Paulo, Brazil; Programa de Pós-graduação Biologia-Química, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo campus Diadema, Rua São Nicolau, 210, Diadema, Brazil
| | - Natasha Ferraz de Campos Reis
- Programa de Pós-graduação Biologia-Química, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo campus Diadema, Rua São Nicolau, 210, Diadema, Brazil; Departamento de Ciências Farmacêuticas, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo campus Diadema
| | | | - Anuska Marcelino Alvares-Saraiva
- Instituto de Ciências da Saúde, Pós-graduação em Patologia Ambiental e Experimental, Universidade Paulista, Rua Bacelar, 902, São Paulo, Brazil; Pós Graduação Interdisciplinar em Saúde, Universidade Cruzeiro do Sul, Rua Galvão Bueno, 868, São Paulo, Brazil; Laboratório de Fisiopatologia, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, Brazil
| | - Patricia Xander
- Programa de Pós-graduação Biologia-Química, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo campus Diadema, Rua São Nicolau, 210, Diadema, Brazil; Departamento de Ciências Farmacêuticas, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo campus Diadema.
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Català C, Velasco-de Andrés M, Casadó-Llombart S, Leyton-Pereira A, Carrillo-Serradell L, Isamat M, Lozano F. Innate immune response to peritoneal bacterial infection. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2022; 371:43-61. [PMID: 35965000 DOI: 10.1016/bs.ircmb.2022.04.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Spontaneous and secondary peritoneal infections, mostly of bacterial origin, easily spread to cause severe sepsis. Cellular and humoral elements of the innate immune system are constitutively present in peritoneal cavity and omentum, and play an important role in peritonitis progression and resolution. This review will focus on the description of the anatomic characteristics of the peritoneal cavity and the composition and function of such innate immune elements under both steady-state and bacterial infection conditions. Potential innate immune-based therapeutic interventions in bacterial peritonitis alternative or adjunctive to classical antibiotic therapy will be briefly discussed.
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Affiliation(s)
- Cristina Català
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | | | - Sergi Casadó-Llombart
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | | | | | - Marcos Isamat
- Sepsia Therapeutics S.L. 08908 L'Hospitalet de Llobregat, Barcelona, Spain
| | - Francisco Lozano
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Servei d'Immunologia, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Barcelona, Spain; Departament de Biomedicina, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
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31
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Elucidating the Role of Innate and Adaptive Immune Responses in the Pathogenesis of Canine Chronic Inflammatory Enteropathy-A Search for Potential Biomarkers. Animals (Basel) 2022; 12:ani12131645. [PMID: 35804545 PMCID: PMC9264988 DOI: 10.3390/ani12131645] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 06/11/2022] [Accepted: 06/14/2022] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Canine chronic inflammatory enteropathy (CIE) is a chronic disease affecting the small or large intestine and, in some cases, the stomach of dogs. This gastrointestinal disorder is common and is characterized by recurrent vomiting, diarrhea, and weight loss in affected dogs. The pathogenesis of IBD is not completely understood. Similar to human IBD, potential disease factors include genetics, environmental exposures, and dysregulation of the microbiota and the immune response. Some important components of the innate and adaptive immune response involved in CIE pathogenesis have been described. However, the immunopathogenesis of the disease has not been fully elucidated. In this review, we summarized the literature associated with the different cell types and molecules involved in the immunopathogenesis of CIE, with the aim of advancing the search for biomarkers with possible diagnostic, prognostic, or therapeutic utility. Abstract Canine chronic inflammatory enteropathy (CIE) is one of the most common chronic gastrointestinal diseases affecting dogs worldwide. Genetic and environmental factors, as well as intestinal microbiota and dysregulated host immune responses, participate in this multifactorial disease. Despite advances explaining the immunological and molecular mechanisms involved in CIE development, the exact pathogenesis is still unknown. This review compiles the latest reports and advances that describe the main molecular and cellular mechanisms of both the innate and adaptive immune responses involved in canine CIE pathogenesis. Future studies should focus research on the characterization of the immunopathogenesis of canine CIE in order to advance the establishment of biomarkers and molecular targets of diagnostic, prognostic, or therapeutic utility.
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Wang J, Lu S, Zheng K, He Z, Li W, Liu J, Guo N, Xie Y, Chen D, Xu M, Wu Y. Treponema pallidum delays the apoptosis of human polymorphonuclear neutrophils through the intrinsic and extrinsic pathways. Mol Immunol 2022; 147:157-169. [PMID: 35597181 DOI: 10.1016/j.molimm.2022.04.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/26/2022] [Accepted: 04/21/2022] [Indexed: 11/26/2022]
Abstract
Treponema pallidum is a "stealth pathogen" responsible for infectious sexually transmitted diseases. Although neutrophils are usually present in skin lesions of early syphilis, the role of these cells in T. pallidum infection has barely been investigated. Neutrophils are short-lived cells that undergo constitutive apoptosis, and phagocytosis usually accelerates this process. Here, we demonstrated that human polymorphonuclear neutrophils (hPMNs) could phagocytose T. pallidum in vitro. An unexpected discovery was that T. pallidum inhibited hPMNs apoptosis markedly in an opsonin-independent manner. Furthermore, this phenomenon was not affected by bacterial viability, as detected by annexin V, morphology studies, and TUNEL staining. Exploration of the underlying mechanism showed that expression of the cleaved forms of caspase-3, -8, and -9 and effector caspase activity were diminished significantly in T. pallidum-infected hPMNs. T. pallidum also impaired staurosporine- and anti-Fas-induced signaling for neutrophil apoptosis. Of note, these effects were accompanied by inducing the autocrine production of the anti-apoptotic cytokine IL-8. Taken together, our data revealed that T. pallidum could inhibit the apoptosis of hPMNs through intrinsic and extrinsic pathways and provide new insights for understanding the pathogenicity mechanisms of T. pallidum.
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Affiliation(s)
- Jianye Wang
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical College, Institution of Pathogenic Biology, University of South China, Hengyang, China
| | - Simin Lu
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical College, Institution of Pathogenic Biology, University of South China, Hengyang, China
| | - Kang Zheng
- Clinical Laboratory, Hengyang Central Hospital, Hengyang, China
| | - Zhangping He
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical College, Institution of Pathogenic Biology, University of South China, Hengyang, China
| | - Weiwei Li
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical College, Institution of Pathogenic Biology, University of South China, Hengyang, China
| | - Jie Liu
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical College, Institution of Pathogenic Biology, University of South China, Hengyang, China
| | - Ningyuan Guo
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical College, Institution of Pathogenic Biology, University of South China, Hengyang, China
| | - Yafeng Xie
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical College, Institution of Pathogenic Biology, University of South China, Hengyang, China; Department of Clinical Laboratory, the Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Dejun Chen
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical College, Institution of Pathogenic Biology, University of South China, Hengyang, China
| | - Man Xu
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical College, Institution of Pathogenic Biology, University of South China, Hengyang, China.
| | - Yimou Wu
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical College, Institution of Pathogenic Biology, University of South China, Hengyang, China.
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Michel V, Berk J, Bozakova N, van der Eijk J, Estevez I, Mircheva T, Relic R, Rodenburg TB, Sossidou EN, Guinebretière M. The Relationships between Damaging Behaviours and Health in Laying Hens. Animals (Basel) 2022; 12:986. [PMID: 35454233 PMCID: PMC9029779 DOI: 10.3390/ani12080986] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 04/01/2022] [Accepted: 04/04/2022] [Indexed: 01/23/2023] Open
Abstract
Since the ban in January 2012 of conventional cages for egg production in the European Union (Council Directive 1999/74/EC), alternative systems such as floor, aviary, free-range, and organic systems have become increasingly common, reaching 50% of housing for hens in 2019. Despite the many advantages associated with non-cage systems, the shift to a housing system where laying hens are kept in larger groups and more complex environments has given rise to new challenges related to management, health, and welfare. This review examines the close relationships between damaging behaviours and health in modern husbandry systems for laying hens. These new housing conditions increase social interactions between animals. In cases of suboptimal rearing and/or housing and management conditions, damaging behaviour or infectious diseases are likely to spread to the whole flock. Additionally, health issues, and therefore stimulation of the immune system, may lead to the development of damaging behaviours, which in turn may result in impaired body conditions, leading to health and welfare issues. This raises the need to monitor both behaviour and health of laying hens in order to intervene as quickly as possible to preserve both the welfare and health of the animals.
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Affiliation(s)
- Virginie Michel
- Direction de la Stratégie et des Programmes, French Agency for Food, Environmental and Occupational Health & Safety (ANSES), 94701 Maisons-Alfort, France
| | - Jutta Berk
- Institute for Animal Welfare and Animal Husbandry, Friedrich-Loeffler-Institut, 29223 Celle, Germany;
| | - Nadya Bozakova
- Department of General Animal Breeding, Animal Hygiene, Ethology and Animal Protection Section, Faculty of Veterinary Medicine, Student’s Campus, Trakia University, 6000 Stara Zagora, Bulgaria;
| | - Jerine van der Eijk
- Animal Health and Welfare, Wageningen Livestock Research, Wageningen University and Research, De Elst 1, 6708 Wageningen, The Netherlands;
| | - Inma Estevez
- Department of Animal Production, Neiker-Basque Institute for Agricultural Research and Development, 01080 Vitoria-Gasteiz, Spain;
| | - Teodora Mircheva
- Section of Biochemistry, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria;
| | - Renata Relic
- Faculty of agriculture, University of Belgrade, 11080 Belgrade, Serbia;
| | - T. Bas Rodenburg
- Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 2, 3584 Utrecht, The Netherlands;
| | - Evangelia N. Sossidou
- Laboratory of Farm Animal Health and Welfare, Veterinary Research Institute, Ellinikos Georgikos Or-Ganismos-DIMITRA (ELGO-DIMITRA), 57001 Thessaloniki, Greece;
| | - Maryse Guinebretière
- Epidemiology, Health and Welfare Unit, French Agency for Food, Environmental and Occupational Health & Safety (ANSES), 22440 Ploufragan, France;
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Kocurova G, Ricny J, Ovsepian SV. Autoantibodies targeting neuronal proteins as biomarkers for neurodegenerative diseases. Theranostics 2022; 12:3045-3056. [PMID: 35547759 PMCID: PMC9065204 DOI: 10.7150/thno.72126] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 03/09/2022] [Indexed: 01/08/2023] Open
Abstract
Neurodegenerative diseases (NDDs) are associated with the accumulation of a range of misfolded proteins across the central nervous system and related autoimmune responses, including the generation of antibodies and the activation of immune cells. Both innate and adaptive immunity become mobilized, leading to cellular and humoral effects. The role of humoral immunity in disease onset and progression remains to be elucidated with rising evidence suggestive of positive (protection, repair) and negative (injury, toxicity) outcomes. In this study, we review advances in research of neuron-targeting autoantibodies in the most prevalent NDDs. We discuss their biological origin, molecular diversity and changes in the course of diseases, consider their relevance to the initiation and progression of pathology as well as diagnostic and prognostic significance. It is suggested that the emerging autoimmune aspects of NDDs not only could facilitate the early detection but also might help to elucidate previously unknown facets of pathobiology with relevance to the development of precision medicine.
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Affiliation(s)
- Gabriela Kocurova
- Experimental Neurobiology Program, National Institute of Mental Health, Klecany, Czech Republic
| | - Jan Ricny
- Experimental Neurobiology Program, National Institute of Mental Health, Klecany, Czech Republic
| | - Saak V. Ovsepian
- Faculty of Science and Engineering, University of Greenwich London, Chatham Maritime, Kent, ME4 4TB, United Kingdom
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Profiling the Murine Acute Phase and Inflammatory Responses to African Snake Venom: An Approach to Inform Acute Snakebite Pathology. Toxins (Basel) 2022; 14:toxins14040229. [PMID: 35448838 PMCID: PMC9028489 DOI: 10.3390/toxins14040229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 03/03/2022] [Accepted: 03/15/2022] [Indexed: 11/17/2022] Open
Abstract
Snake envenoming causes rapid systemic and local effects that often result in fatal or long-term disability outcomes. It seems likely that acute phase and inflammatory responses contribute to these haemorrhagic, coagulopathic, neurotoxic, nephrotoxic and local tissue destructive pathologies. However, the contributory role of acute phase/inflammatory responses to envenoming is under-researched and poorly understood—particularly for envenoming by sub-Saharan African venomous snakes. To provide data to help guide future studies of human patients, and to explore the rationale for adjunct anti-inflammatory medication, here we used an in vivo murine model to systematically assess acute phase and inflammatory responses of mice to ten African snake venoms. In addition to investigating snake species-specific effects of venom on the cardiovascular system and other key organs and tissues, we examined the response to intravascular envenoming by acute phase reactants, including serum amyloid A, P-selectin and haptoglobin, and several cytokines. Venoms of the spitting (Naja nigricollis) and forest (N. melanoleuca) cobras resulted in higher acute phase and inflammatory responses than venoms from the other cobras, mambas and vipers tested. Naja nigricollis venom also stimulated a 100-fold increase in systemic interleukin 6. Thin blood films from venom-treated mice revealed species-specific changes in red blood cell morphology, indicative of membrane abnormalities and functional damage, lymphopenia and neutrophil leukocytosis. Our ex vivo assays with healthy human blood treated with these venoms identified that N. nigricollis venom induced marked levels of haemolysis and platelet aggregation. We conclude that African snake venoms stimulate very diverse responses in this mouse model of acute systemic envenoming, and that venoms of the African cobras N. nigricollis and N. melanoleuca, in particular, cause marked inflammatory and non-specific acute phase responses. We also report that several African snake venoms cause haemolytic changes. These findings emphasise the importance of understanding acute responses to envenoming, and that further research in this area may facilitate new diagnostic and treatment approaches, which in turn may lead to better clinical outcomes for snakebite patients.
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Altvater-Hughes TE, Hodgins DC, Wagter-Lesperance L, Beard SC, Cartwright SL, Mallard BA. Concentration and heritability of immunoglobulin G and natural antibody immunoglobulin M in dairy and beef colostrum along with serum total protein in their calves. J Anim Sci 2022; 100:skac006. [PMID: 35022742 PMCID: PMC8867588 DOI: 10.1093/jas/skac006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 01/10/2022] [Indexed: 11/13/2022] Open
Abstract
Immunoglobulin (Ig) G and natural antibody (NAb) IgM are passively transferred to the neonatal calf through bovine colostrum. Maternal IgG provides pathogen- or vaccine-specific protection and comprises about 85% of colostral Ig. NAb-IgM is less abundant but provides broad and nonspecific reactivity, potentially contributing to protection against the dissemination of pathogens in the blood (septicemia) in a calf's first days of life. In the dairy and beef industries, failure of passive transfer (FPT) of colostral Ig (serum total protein [STP] <5.2 g/dL) is still a common concern. The objectives of this study were to: (1) compare colostral IgG concentrations and NAb-IgM titers between dairy and beef cows; (2) assess the effect of beef breed on colostral IgG; (3) compare passive transfer of colostral Ig in dairy and beef calves; and (4) estimate the heritability of colostral IgG and NAb-IgM. Colostrum was collected from Holstein dairy (n = 282) and crossbred beef (n = 168) cows at the University of Guelph dairy and beef research centers. Colostral IgG was quantified by radial immunodiffusion and NAb-IgM was quantified by an enzyme-linked immunosorbent assay. In dairy (n = 308) and beef (n = 169) calves, STP was estimated by digital refractometry. Beef cows had significantly greater colostral IgG (146.5 ± 9.5 standard error of the mean [SEM] g/L) than dairy cows (92.4 ± 5.2 g/L, P <0.01). Beef cows with a higher proportion of Angus ancestry had significantly lower colostral IgG (125.5 ± 5.8 g/L) than cows grouped as "Other" (142.5 ± 4.9 g/L, P = 0.02). Using the FPT cutoff, 13% of dairy and 16% of beef calves had FPT; still, beef calves had a significantly larger proportion with excellent passive transfer (STP ≥6.2 g/dL, P <0.01). The heritability of colostral IgG was 0.04 (±0.14) in dairy and 0.14 (±0.32) in beef. Colostral NAb-IgM titers in dairy (12.12 ± 0.22, log2 [reciprocal of titer]) and beef cows (12.03 ± 0.19) did not differ significantly (P = 0.71). The range of NAb-IgM titers was 9.18-14.60, equivalent to a 42-fold range in antibody concentration. The heritability of colostral NAb was 0.24 (±0.16) in dairy and 0.11 (±0.19) in beef cows. This study is the first to compare colostral NAb-IgM between dairy and beef cows. Based on the range in NAb-IgM titers and the heritability, selective breeding may improve colostrum quality and protection for neonatal calves in the early days of life.
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Affiliation(s)
- Tess E Altvater-Hughes
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1, Canada
| | - Douglas C Hodgins
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1, Canada
| | - Lauraine Wagter-Lesperance
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1, Canada
| | - Shannon C Beard
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1, Canada
| | - Shannon L Cartwright
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1, Canada
| | - Bonnie A Mallard
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1, Canada
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Huska B, Kubinec C, Sadarangani M, Ulanova M. Seroprevalence of IgG and IgM antibodies to Haemophilus influenzae type a in Canadian children. Vaccine 2022; 40:1128-1134. [PMID: 35078664 DOI: 10.1016/j.vaccine.2022.01.029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 12/21/2021] [Accepted: 01/13/2022] [Indexed: 10/19/2022]
Abstract
BACKGROUND Over the last 2 decades, Haemophilus influenzae type a (Hia) has emerged as a significant cause of invasive disease in some geographic regions and populations. Recognition of the importance of Hia in the etiology of serious disease, particularly in young children, prompted the development of a new protein-capsular polysaccharide conjugate vaccine, similar in design to a vaccine against H. influenzae type b. At present, understanding of Hia immunology is incomplete; the immunological correlate of protection against invasive disease is unknown. METHODS Our objective was to study Hia antibody in children of various ages residing in a Canadian province with low incidence rates of invasive disease. The enzyme-linked immunosorbent assays were performed to quantify plasma IgG and IgM specific to Hia capsular polysaccharide in 133 children (3 months to 16 years). RESULTS Both anti-Hia IgG and IgM concentrations increased with age and were significantly higher in older children; a positive correlation between age and concentrations of Hia antibody was found. IgM antibody concentrations were significantly higher than IgG, with mean IgM concentrations over 10 times larger than IgG across all age groups. CONCLUSIONS The steady rise of naturally acquired, Hia-specific IgG and IgM concentrations in a pediatric population with low incidence rates of invasive Hia disease suggests the exposure to some cross-reactive environmental antigens as a major source of the antibody. However, the carriage rates of Hia in the region are unknown and further seroepidemiological studies are warranted. Although natural antibody may protect certain population groups against invasive disease, immunization of younger children will be essential to prevent serious infections if Hia continues to spread across North America.
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Affiliation(s)
- Brenda Huska
- Northern Ontario School of Medicine, Thunder Bay, ON, Canada
| | - Chelsea Kubinec
- Northern Ontario School of Medicine, Thunder Bay, ON, Canada
| | - Manish Sadarangani
- Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
| | - Marina Ulanova
- Northern Ontario School of Medicine, Thunder Bay, ON, Canada.
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Dahmani M, Cook JH, Zhu JC, Riley SP. Contribution of classical complement activation and IgM to the control of Rickettsia infection. Mol Microbiol 2021; 116:1476-1488. [PMID: 34725868 PMCID: PMC8955150 DOI: 10.1111/mmi.14839] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 10/28/2021] [Accepted: 10/29/2021] [Indexed: 01/02/2023]
Abstract
Pathogenic Rickettsia are obligate intracellular bacteria and the etiologic agents of many life‐threatening infectious diseases. Due to the serious nature of these infections, it is imperative to both identify the responsive immune sensory pathways and understand the associated immune mechanisms that restrict Rickettsia proliferation. Previous studies have demonstrated that the mammalian complement system is both activated during Rickettsia infection and contributes to the immune response to infection. To further define this component of the mammalian anti‐Rickettsia immune response, we sought to identify the mechanism(s) of complement activation during Rickettsia infection. We have employed a series of in vitro and in vivo models of infection to investigate the role of the classical complement activation pathway during Rickettsia infection. Depletion or elimination of complement activity demonstrates that both C1q and pre‐existing IgM contribute to complement activation; thus implicating the classical complement system in Rickettsia‐mediated complement activation. Elimination of the classical complement pathway from mice increases susceptibility to R. australis infection with both increased bacterial loads in multiple tissues and decreased immune activation markers. This study highlights the role of the classical complement pathway in immunity against Rickettsia and implicates resident Rickettsia‐responsive IgM in the response to infection.
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Affiliation(s)
- Mustapha Dahmani
- Department of Veterinary Medicine, University of Maryland-College Park, College Park, Maryland, USA.,Virginia-Maryland College of Veterinary Medicine, College Park, Maryland, USA
| | - Jack H Cook
- Department of Veterinary Medicine, University of Maryland-College Park, College Park, Maryland, USA.,Virginia-Maryland College of Veterinary Medicine, College Park, Maryland, USA
| | - Jinyi C Zhu
- Department of Veterinary Medicine, University of Maryland-College Park, College Park, Maryland, USA.,Virginia-Maryland College of Veterinary Medicine, College Park, Maryland, USA
| | - Sean P Riley
- Department of Veterinary Medicine, University of Maryland-College Park, College Park, Maryland, USA.,Virginia-Maryland College of Veterinary Medicine, College Park, Maryland, USA
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Ahmed AR, Aksoy M. IgM Deficiency in Autoimmune Blistering Mucocutaneous Diseases Following Various Treatments: Long Term Follow-Up and Relevant Observations. Front Immunol 2021; 12:727520. [PMID: 34646266 PMCID: PMC8504479 DOI: 10.3389/fimmu.2021.727520] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 09/01/2021] [Indexed: 11/13/2022] Open
Abstract
IgM deficiency has been reported in patients with many autoimmune diseases treated with Rituximab (RTX). It has not been studied, in detail, in autoimmune mucocutaneous blistering diseases (AIMBD). Our objectives were: (i) Examine the dynamics of IgM levels in patients with and without RTX. (ii) Influence of reduced serum IgM levels on clinical and laboratory parameters. (iii) Explore the possible molecular and cellular basis for reduced serum IgM levels. This retrospective study that was conducted in a single-center from 2000 to 2020. Serial IgM levels were studied in 348 patients with five AIMBD (pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid, and ocular cicatricial pemphigoid) and found decreased in 55 patients treated with RTX, IVIG, and conventional immunosuppressive therapy (CIST). Hence the incidence of decreased serum IgM is low. The incidence of decreased IgM in patients treated with RTX was 19.6%, in patients treated with IVIG and CIST, it was 52.8% amongst the 55 patients. IgM levels in the post-RTX group were statistically significantly different from the IVIG group (p<0.018) and CIST group (p<0.001). There were no statistically significant differences between the groups in other clinical and laboratory measures. Decreased serum IgM did not affect depletion or repopulation of CD19+ B cells. Patients in the three groups achieved clinical and serological remission, in spite of decreased IgM levels. Decrease in IgM was isolated, since IgG and IgA were normal throughout the study period. Decreased IgM persisted at the same level, while the patients were in clinical remission, for several years. In spite of persistent decreased IgM levels, the patients did not develop infections, tumors, other autoimmune diseases, or warrant hospitalization. Studies on IgM deficiency in knockout mice provided valuable insights. There is no universally accepted mechanism that defines decreased IgM levels in AIMBD. The data is complex, multifactorial, sometimes contradictory, and not well understood. Nonetheless, data in this study provides novel information that enhances our understanding of the biology of IgM in health and disease.
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Affiliation(s)
- A. Razzaque Ahmed
- Department of Dermatology, The Center for Blistering Diseases, Tufts University School of Medicine, Boston, MA, United States
- Dermatology Service, Boston Veterans Administration Health Services, Boston, MA, United States
| | - Merve Aksoy
- Department of Dermatology, The Center for Blistering Diseases, Tufts University School of Medicine, Boston, MA, United States
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Suchocki T, Czech B, Dunislawska A, Slawinska A, Derebecka N, Wesoly J, Siwek M, Szyda J. SNP prioritization in targeted sequencing data associated with humoral immune responses in chicken. Poult Sci 2021; 100:101433. [PMID: 34551372 PMCID: PMC8458985 DOI: 10.1016/j.psj.2021.101433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 07/13/2021] [Accepted: 08/15/2021] [Indexed: 11/30/2022] Open
Abstract
Our study aimed to identify single nucleotide polymorphisms (SNPs) with a significant impact on the innate immunity represented by antibody response against lipopolysaccharide (LPS) and lipoteichoid acid (LTA) and the adaptive immune response represented toward keyhole limpet hemocyanin (KLH) using the SNP prioritization method. Data set consisted of 288 F2 experimental individuals, created by crossing Green-legged Partridgelike and White Leghorn. The analyzed SNPs were located within 24 short genomic regions of GGA1, GGA2, GGA3, GGA4, GGA9, GGA10, GGA14, GGA18, and GGZ, pre-targeted based on literature references and database information. For the specific antibody response toward KLH at d 0 the most highly prioritized SNP for additive and dominance effects were located on GGA2 in the 3’UTR of MYD88. For the response at d 7, the most highly prioritized SNP pointed at the 3’UTR of MYD88, but potential causal additive variants were located within ADIPOQ and one in PROCR. The highest priority for additive and dominance effects in the antibody response toward lipoteichoic acid at d 0 was attributed to the same SNP, located on GGA2 in the 3’UTR region of MYD88. Two SNPs among the top-10 for additive effect were located in the exon of NOCT. SNPs selected for their additive effect on antibody response toward lipopolysaccharide at d 0 marked 3 genes – NOCT, MYD88, and SNX8, while SNPs selected for their dominance effect marked – NOCT, ADIPOQ, and MYD88. The top-10 variants identified in our study were located in different functional parts of the genome. In the context of causality three groups can be distinguished: variants located in exons of protein coding genes (ADIPOQ, NOCT, PROCR, SNX8), variants within exons of non-coding transcripts, and variants located in genes’ UTR regions. Variants from the first group influence protein structure and variants from both latter groups’ exhibit regulatory roles on DNA (UTR) or RNA (lncRNA).
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Affiliation(s)
- Tomasz Suchocki
- Biostatistics Group, Department of Genetics, Wrocław University of Environmental and Life Sciences, Wrocław, Poland; National Research Institute of Animal Production, Balice, Poland
| | - Bartosz Czech
- Biostatistics Group, Department of Genetics, Wrocław University of Environmental and Life Sciences, Wrocław, Poland
| | - Aleksandra Dunislawska
- Department of Animal Biotechnology and Genetics, UTP University of Science and Technology, Bydgoszcz 85-084, Poland
| | - Anna Slawinska
- Department of Animal Biotechnology and Genetics, UTP University of Science and Technology, Bydgoszcz 85-084, Poland
| | - Natalia Derebecka
- Laboratory of High Throughput Technologies, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland
| | - Joanna Wesoly
- Laboratory of High Throughput Technologies, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland
| | - Maria Siwek
- Department of Animal Biotechnology and Genetics, UTP University of Science and Technology, Bydgoszcz 85-084, Poland.
| | - Joanna Szyda
- Biostatistics Group, Department of Genetics, Wrocław University of Environmental and Life Sciences, Wrocław, Poland; National Research Institute of Animal Production, Balice, Poland
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Tisagenlecleucel Immunogenicity in Relapsed/Refractory Acute Lymphoblastic Leukemia and Diffuse Large B-Cell Lymphoma. Blood Adv 2021; 5:4980-4991. [PMID: 34432863 PMCID: PMC9153050 DOI: 10.1182/bloodadvances.2020003844] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 04/16/2021] [Indexed: 11/20/2022] Open
Abstract
Pre- and posttreatment anti-mCAR19 antibodies did not alter tisagenlecleucel cellular kinetics, efficacy, or safety in r/r B-ALL or r/r DLBCL. T-cell responses to mCAR19 peptides did not influence patient outcomes or cellular expansion in r/r B-ALL or r/r DLBCL. Tisagenlecleucel is indicated for pediatric and young adult patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) and adult patients with r/r diffuse large B-cell lymphoma (DLBCL). The tisagenlecleucel chimeric antigen receptor (CAR) contains a murine single-chain variable fragment domain; we examined the effects of humoral and cellular immune responses to tisagenlecleucel on clinical outcomes using 2 validated assays. Data were pooled from the ELIANA (registered at www.clinicaltrials.gov as #NCT02435849) and ENSIGN (#NCT02228096) trials in r/r B-ALL (N = 143) and the JULIET trial (#NCT02445248) in r/r DLBCL (N = 115). Humoral responses were determined by flow cytometric measurement of anti-murine CAR19 (mCAR19) antibodies in serum. Cellular responses were determined using T-cell production of interferon-γ in response to 2 different pools of mCAR19 peptides. Pretreatment anti-mCAR19 antibodies were detected in 81% of patients with r/r B-ALL and 94% of patients with r/r DLBCL. Posttreatment anti-mCAR19 antibodies were higher than patient-specific baseline in 42% of r/r B-ALL and 9% of r/r DLBCL patients. Pretreatment and posttreatment anti-mCAR19 antibodies did not affect tisagenlecleucel cellular kinetics, including maximum concentration and persistence (r2 < 0.05), clinical response (day-28 response, duration of response, and event-free survival), and safety. T-cell responses were consistent over time, with net responses <1% at baseline and posttreatment time points in a majority of patients and no effect on transgene expansion or persistence or outcomes. Presence of baseline and/or posttreatment anti-mCAR19 antibodies or T-cell responses did not alter the activity of tisagenlecleucel in patients with r/r B-ALL or r/r DLBCL.
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IgM Immunoglobulin Influences Recovery after Cervical Spinal Cord Injury by Modulating the IgG Autoantibody Response. eNeuro 2021; 8:ENEURO.0491-19.2021. [PMID: 34413082 PMCID: PMC8431822 DOI: 10.1523/eneuro.0491-19.2021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 06/06/2021] [Accepted: 06/10/2021] [Indexed: 12/24/2022] Open
Abstract
Spinal cord injury (SCI) results in the development of detrimental autoantibodies against the lesioned spinal cord. IgM immunoglobulin maintains homeostasis against IgG-autoantibody responses, but its effect on SCI recovery remains unknown. In the present study we investigated the role of IgM immunoglobulin in influencing recovery after SCI. To this end, we induced cervical SCI at the C6/C7 level in mice that lacked secreted IgM immunoglobulin [IgM-knock-out (KO)] and their wild-type (WT) littermate controls. Overall, the absence of secretory IgM resulted in worse outcomes as compared with WT mice with SCI. At two weeks after injury, IgM-KO mice had significantly more IgG antibodies, which fixed the complement system, in the injured spinal cord parenchyma. In addition to these findings, IgM-KO mice had more parenchymal T-lymphocytes as well as CD11b+ microglia/macrophages, which co-localized with myelin. At 10 weeks after injury, IgM-KO mice showed significant impairment in neurobehavioral recovery, such as deteriorated coordination, reduced hindlimb swing speed and print area. These neurobehavioral detriments were coupled with increased lesional tissue and myelin loss. Taken together, this study provides the first evidence for the importance of IgM immunoglobulin in modulating recovery after SCI and suggests that modulating IgM could be a novel therapeutic approach to enhance recovery after SCI.
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Clemens EA, Alexander-Miller MA. Understanding Antibody Responses in Early Life: Baby Steps towards Developing an Effective Influenza Vaccine. Viruses 2021; 13:v13071392. [PMID: 34372597 PMCID: PMC8310046 DOI: 10.3390/v13071392] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 07/13/2021] [Indexed: 01/01/2023] Open
Abstract
The immune system of young infants is both quantitatively and qualitatively distinct from that of adults, with diminished responsiveness leaving these individuals vulnerable to infection. Because of this, young infants suffer increased morbidity and mortality from respiratory pathogens such as influenza viruses. The impaired generation of robust and persistent antibody responses in these individuals makes overcoming this increased vulnerability through vaccination challenging. Because of this, an effective vaccine against influenza viruses in infants under 6 months is not available. Furthermore, vaccination against influenza viruses is challenging even in adults due to the high antigenic variability across viral strains, allowing immune evasion even after induction of robust immune responses. This has led to substantial interest in understanding how specific antibody responses are formed to variable and conserved components of influenza viruses, as immune responses tend to strongly favor recognition of variable epitopes. Elicitation of broadly protective antibody in young infants, therefore, requires that both the unique characteristics of young infant immunity as well as the antibody immunodominance present among epitopes be effectively addressed. Here, we review our current understanding of the antibody response in newborns and young infants and discuss recent developments in vaccination strategies that can modulate both magnitude and epitope specificity of IAV-specific antibody.
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Riba M, Augé E, Tena I, Del Valle J, Molina-Porcel L, Ximelis T, Vilaplana J, Pelegrí C. Corpora Amylacea in the Human Brain Exhibit Neoepitopes of a Carbohydrate Nature. Front Immunol 2021; 12:618193. [PMID: 34262556 PMCID: PMC8273382 DOI: 10.3389/fimmu.2021.618193] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 06/10/2021] [Indexed: 11/23/2022] Open
Abstract
Corpora amylacea (CA) in the human brain are polyglucosan bodies that accumulate residual substances originated from aging and both neurodegenerative and infectious processes. These structures, which act as waste containers, are released from the brain to the cerebrospinal fluid, reach the cervical lymph nodes via the meningeal lymphatic system and may be phagocytosed by macrophages. Recent studies indicate that CA present certain neoepitopes (NEs) that can be recognized by natural antibodies of the IgM class, and although evidence of different kinds suggests that these NEs may be formed by carbohydrate structures, their precise nature is unknown. Here, we adapted standard techniques to examine this question. We observed that the preadsorption of IgMs with specific carbohydrates has inhibitory effects on the interaction between IgMs and CA, and found that the digestion of CA proteins had no effect on this interaction. These findings point to the carbohydrate nature of the NEs located in CA. Moreover, the present study indicates that, in vitro, the binding between certain natural IgMs and certain epitopes may be disrupted by certain monosaccharides. We wonder, therefore, whether these inhibitions may also occur in vivo. Further studies should now be carried out to assess the possible in vivo effect of glycemia on the reactivity of natural IgMs and, by extension, on natural immunity.
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Affiliation(s)
- Marta Riba
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Barcelona, Spain.,Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.,Centros de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | - Elisabet Augé
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Barcelona, Spain.,Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.,Centros de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | - Iraida Tena
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Barcelona, Spain
| | - Jaume Del Valle
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Barcelona, Spain.,Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.,Centros de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | - Laura Molina-Porcel
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.,Neurological Tissue Bank, Biobanc-Hospital Clínic-IDIBAPS, Barcelona, Spain
| | - Teresa Ximelis
- Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.,Neurological Tissue Bank, Biobanc-Hospital Clínic-IDIBAPS, Barcelona, Spain
| | - Jordi Vilaplana
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Barcelona, Spain.,Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.,Centros de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | - Carme Pelegrí
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Barcelona, Spain.,Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.,Centros de Biomedicina en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
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Annamalai B, Parsons N, Nicholson C, Joseph K, Coughlin B, Yang X, Jones BW, Tomlinson S, Rohrer B. Natural immunoglobulin M-based delivery of a complement alternative pathway inhibitor in mouse models of retinal degeneration. Exp Eye Res 2021; 207:108583. [PMID: 33878326 PMCID: PMC8504679 DOI: 10.1016/j.exer.2021.108583] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 03/31/2021] [Accepted: 04/13/2021] [Indexed: 11/23/2022]
Abstract
PURPOSE Age-related macular degeneration is a slowly progressing disease. Studies have tied disease risk to an overactive complement system. We have previously demonstrated that pathology in two mouse models, the choroidal neovascularization (CNV) model and the smoke-induced ocular pathology (SIOP) model, can be reduced by specifically inhibiting the alternative complement pathway (AP). Here we report on the development of a novel injury-site targeted inhibitor of the alternative pathway, and its characterization in models of retinal degeneration. METHODS Expression of the danger associated molecular pattern, a modified annexin IV, in injured ARPE-19 cells was confirmed by immunohistochemistry and complementation assays using B4 IgM mAb. Subsequently, a construct was prepared consisting of B4 single chain antibody (scFv) linked to a fragment of the alternative pathway inhibitor, fH (B4-scFv-fH). ARPE-19 cells stably expressing B4-scFv-fH were microencapsulated and administered intravitreally or subcutaneously into C57BL/6 J mice, followed by CNV induction or smoke exposure. Progression of CNV was analyzed using optical coherence tomography, and SIOP using structure-function analyses. B4-scFv-fH targeting and AP specificity was assessed by Western blot and binding experiments. RESULTS B4-scFv-fH was secreted from encapsulated RPE and inhibited complement in RPE monolayers. B4-scFv-fH capsules reduced CNV and SIOP, and western blotting for breakdown products of C3α, IgM and IgG confirmed a reduction in complement activation and antibody binding in RPE/choroid. CONCLUSIONS Data supports a role for natural antibodies and neoepitope expression in ocular disease, and describes a novel strategy to target AP-specific complement inhibition to diseased tissue in the eye. PRECIS AMD risk is tied to an overactive complement system, and ocular injury is reduced by alternative pathway (AP) inhibition in experimental models. We developed a novel inhibitor of the AP that targets an injury-specific danger associated molecular pattern, and characterized it in disease models.
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Affiliation(s)
| | - Nathaniel Parsons
- Department of Ophthalmology, Medical University of South Carolina, Charleston, SC, USA
| | - Crystal Nicholson
- Department of Ophthalmology, Medical University of South Carolina, Charleston, SC, USA
| | - Kusumam Joseph
- Department of Ophthalmology, Medical University of South Carolina, Charleston, SC, USA
| | - Beth Coughlin
- Department of Ophthalmology, Medical University of South Carolina, Charleston, SC, USA
| | - Xiaofeng Yang
- Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA
| | - Bryan W Jones
- Department of Ophthalmology, University of Utah, Salt Lake City, UT, USA
| | - Stephen Tomlinson
- Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Medical Center, Division of Research, Charleston, SC, USA
| | - Bärbel Rohrer
- Department of Ophthalmology, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Medical Center, Division of Research, Charleston, SC, USA; Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
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Vlachonikola E, Sofou E, Chatzidimitriou A, Stamatopoulos K, Agathangelidis A. The Significance of B-cell Receptor Stereotypy in Chronic Lymphocytic Leukemia: Biological and Clinical Implications. Hematol Oncol Clin North Am 2021; 35:687-702. [PMID: 34174980 DOI: 10.1016/j.hoc.2021.03.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The finding that (quasi)identical, stereotyped B-cell receptor (BcR) immunoglobulins IGs) are expressed in a significant fraction of chronic lymphocytic leukemia (CLL) highlighted the importance of antigen selection in disease pathogenesis. Subsets of patients sharing the same stereotyped BcR IG display consistent biological features and, at least for certain subsets, clinical presentation and outcome, including the response to particular treatment. On these grounds, BcR IG stereotypy emerges as a useful tool for dissecting the pronounced heterogeneity of CLL toward refining risk stratification and therapeutic management aligned with the principles of precision medicine.
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Affiliation(s)
- Elisavet Vlachonikola
- Institute of Applied Biosciences, Centre for Research and Technology Hellas, 6th km Charilaou - Thermis, 57001 Thermi, Thessaloniki, Greece; Department of Genetics and Molecular Biology, Faculty of Biology, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Electra Sofou
- Institute of Applied Biosciences, Centre for Research and Technology Hellas, 6th km Charilaou - Thermis, 57001 Thermi, Thessaloniki, Greece; Laboratory of Biological Chemistry, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Anastasia Chatzidimitriou
- Institute of Applied Biosciences, Centre for Research and Technology Hellas, 6th km Charilaou - Thermis, 57001 Thermi, Thessaloniki, Greece; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala 75236, Sweden
| | - Kostas Stamatopoulos
- Institute of Applied Biosciences, Centre for Research and Technology Hellas, 6th km Charilaou - Thermis, 57001 Thermi, Thessaloniki, Greece; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala 75236, Sweden.
| | - Andreas Agathangelidis
- Institute of Applied Biosciences, Centre for Research and Technology Hellas, 6th km Charilaou - Thermis, 57001 Thermi, Thessaloniki, Greece
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Kaçar C, Kaya S, Kuru M, Erkılıç EE, Öğün M, Oral H, Demir MC. Determination of natural antibodies, beta-hydroxybutyric acid, and non-esterified fatty acid levels in the serum of peripartum Tuj and Hemşin sheep. Vet World 2021; 14:1002-1006. [PMID: 34083952 PMCID: PMC8167533 DOI: 10.14202/vetworld.2021.1002-1006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 03/04/2021] [Indexed: 11/22/2022] Open
Abstract
Background and Aim: Many metabolic and immunological changes occur during the transition period. Innate immunity plays an important role against to infections and natural antibodies (NAb) are important in immunity. This study aims to determine a connection between serum NAb titers, beta-hydroxybutyric acid (BHBA), and non-esterified fatty acid (NEFA) concentrations in Tuj and Hemşin sheep during the peripartum period. Materials and Methods: Serum NAb, BHBA, and NEFA levels were determined from the blood samples collected from Tuj and Hemşin sheep on days 30 and 15 before birth, on the day of birth (day 0), and on days 15 and 30 after birth. Results: NAb titers were found to be higher in Tuj than in Hemşin sheep (p<0.001). No statistically significant difference was found in serum BHBA concentrations of both breeds on all sampling days (p>0.05). The serum NEFA level was lower in Tuj sheep in the last 15 days of pregnancy compared to Hemşin sheep (p<0.05), while no difference was found in samples collected at the other time points. Conclusion: This study indicated that serum NAb titers significantly changed in Tuj and Hemşin sheep during the transition period. Serum BHBA and NEFA concentrations increased during the last stages of pregnancy and decreased after birth. Based on these findings, it is suggested that the immunological status could vary by the breed of sheep or various factors that affect the sheep’s metabolic state.
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Affiliation(s)
- Cihan Kaçar
- Department of Obstetrics and Gynecology, Faculty of Veterinary Medicine, Kafkas University, 36100 Kars, Turkey
| | - Semra Kaya
- Department of Obstetrics and Gynecology, Faculty of Veterinary Medicine, Kafkas University, 36100 Kars, Turkey
| | - Mushap Kuru
- Department of Obstetrics and Gynecology, Faculty of Veterinary Medicine, Kafkas University, 36100 Kars, Turkey
| | - Ekin Emre Erkılıç
- Department of Internal Medicine, Faculty of Veterinary Medicine, Kafkas University, 36100 Kars, Turkey
| | - Metin Öğün
- Department of Biochemistry, Faculty of Medicine, Kafkas University, 36100 Kars, Turkey
| | - Hasan Oral
- Department of Obstetrics and Gynecology, Faculty of Veterinary Medicine, Kafkas University, 36100 Kars, Turkey
| | - Murat Can Demir
- Department of Obstetrics and Gynecology, Faculty of Veterinary Medicine, Kafkas University, 36100 Kars, Turkey
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Mosaed M, Pourfathollah AA, Moghadam M, Jazayeri MH, Safdarian AR. Evaluation of serum natural autoantibodies reaction in different hematological disorders with prospective view to their probable utilization in predictive medicine. Asian J Transfus Sci 2021; 14:167-171. [PMID: 33767544 PMCID: PMC7983152 DOI: 10.4103/ajts.ajts_15_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Accepted: 11/24/2017] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND There are some antibodies which are present in healthy individuals without any former exposure to foreign antigens; they are known as natural autoantibodies (NAAbs). In recent years, it was shown that they probably contribute to the homeostasis of the whole body and might be present before beginning of some diseases. Thus, as new biomarkers, they are promising factors to diagnose diseases. MATERIALS AND METHODS In this study, we drew upon samples of 924 individuals (600 controls and 324 cases) with underlying diseases of anemia, polycythemia, leukocytosis, thrombocytopenia, thrombocytosis, and pancytopenia. For detection of NAAbs against red blood cell, plasma samples were incubated with their own red cell suspension in 4°C for 18 h. Then, positive samples were evaluated for antibody screening and titration. RESULTS Fifty-two (8.6%) controls and 58 (17.9%) cases showed positive reaction (Pv < 0.001). The prevalence of positive antibody screens among auto-positive controls was 53% and 100% among cases; moreover, strength of antibody screen reaction had a mean rank of 22.5 in controls and a mean rank of 38.5 in cases (Pv < 0.001). A significant relation was also observed between ABO blood group and prevalence of NAAbs in controls but not in cases (Pv < 0.05). CONCLUSION The prevalence and potency of NAAbs increased along with hematological changes; moreover, the antibody reactions' pattern and titration showed significant differences between the two groups and these may be useful as biomarker for monitoring and prediction of some hematological diseases.
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Affiliation(s)
- Maryam Mosaed
- Iran Blood Transfusion Research Center, Tarbiat Modares University, Tehran, Iran
| | | | | | - Mir Hadi Jazayeri
- Department of Immunology, Iran University of Medical Sciences, Tehran, Iran
| | - Amir Reza Safdarian
- Department of Immunology, Medical Faculty, Tarbiat Modares University, Tehran, Iran
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Jaufmann J, Tümen L, Beer-Hammer S. SLy2-overexpression impairs B-cell development in the bone marrow and the IgG response towards pneumococcal conjugate-vaccine. IMMUNITY INFLAMMATION AND DISEASE 2021; 9:533-546. [PMID: 33592135 PMCID: PMC8127564 DOI: 10.1002/iid3.413] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 01/08/2021] [Accepted: 02/02/2021] [Indexed: 12/12/2022]
Abstract
Background Infections with Streptococcus pneumoniae can cause severe diseases in humans including pneumonia. Although guidelines for vaccination have been established, S. pneumoniae is still responsible for a serious burden of disease around the globe. Currently, two pneumococcal immunizations are available, namely the pure polysaccharide vaccine Pneumovax23 (P23) and the conjugate‐vaccine Prevenar13 (PCV13). We recently reported impaired thymus‐independent antibody responses towards P23 in mice overexpressing the immunoinhibitory adapter SLy2. The purpose of this study was to evaluate adaptive B‐cell responses towards the thymus‐dependent vaccine PCV13 in SLy2‐overexpressing mice and to study their survival rate during pneumococcal lung infection. Moreover, we investigated B‐cell developmental stages within the bone marrow (BM) in the context of excessive SLy2‐expression. Methods B‐cell subsets and their surface immune globulins were investigated by flow cytometry. For class‐switch assays, isolated splenic B cells were stimulated in vitro with lipopolysaccharide and interleukin‐4 and antibody secretion was quantified via LEGENDplex. To study PCV13‐specific responses, mice were immunized and serum antibody titers (immunoglobulin M, immunoglobulins IgG1, IgG2, and IgG3) were examined by enzyme‐linked immunosorbent assay. Survival rates of mice were assessed within 7 days upon intranasal challenge with S. pneumoniae. Results Our data demonstrate impaired IgG1 and IgG3 antibody responses towards the pneumococcal conjugate‐vaccine PCV13 in SLy2‐overexpressing mice. This was accompanied by reduced frequencies and numbers of BM‐resident plasmablasts. In addition, we found drastically reduced counts of B‐cell precursors in the BM of SLy2‐Tg mice. The survival rate upon intranasal challenge with S. pneumoniae was mostly comparable between the genotypes. Conclusion Our findings demonstrate an important role of the adapter protein SLy2 in the context of adaptive antibody responses against pneumococcal conjugate‐vaccine. Interestingly, deficits in humoral immunity seemed to be compensated by cellular immune effectors upon bacterial challenge. Our study further shows a novel relevance of SLy2 for plasmablasts and B‐cell progenitors in the BM.
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Affiliation(s)
- Jennifer Jaufmann
- Department of Pharmacology, Experimental Therapy and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomik and ICePhA, University of Tuebingen, Tuebingen, Germany
| | - Leyla Tümen
- Department of Pharmacology, Experimental Therapy and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomik and ICePhA, University of Tuebingen, Tuebingen, Germany
| | - Sandra Beer-Hammer
- Department of Pharmacology, Experimental Therapy and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomik and ICePhA, University of Tuebingen, Tuebingen, Germany
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LaVere AA, Hamlin HJ, Lowers RH, Parrott BB, Ezenwa VO. Associations between testosterone and immune activity in alligators depend on bacteria species and temperature. Funct Ecol 2021. [DOI: 10.1111/1365-2435.13756] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
| | | | - Russell H. Lowers
- Herndon Solutions Group, LLC, NASA Environmental and Medical Contract Kennedy Space Center FL USA
| | - Benjamin B. Parrott
- Odum School of Ecology University of Georgia Athens GA USA
- Savannah River Ecology Laboratory University of Georgia Aiken SC USA
| | - Vanessa O. Ezenwa
- Odum School of Ecology University of Georgia Athens GA USA
- Department of Infectious Diseases College of Veterinary Medicine University of Georgia Athens GA USA
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