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Piccioni A, Cicchinelli S, Valletta F, De Luca G, Longhitano Y, Candelli M, Ojetti V, Sardeo F, Navarra S, Covino M, Franceschi F. Gut Microbiota and Autoimmune Diseases: A Charming Real World Together with Probiotics. Curr Med Chem 2022; 29:3147-3159. [PMID: 34551690 DOI: 10.2174/0929867328666210922161913] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 07/28/2021] [Accepted: 08/18/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND The role of gut microbiota in human disease is fascinating for hundreds of researchers worldwide. Many works have highlighted that gut microbiota modulates the immune system and that its disruption can trigger autoimmune and inflammatory immune-mediated diseases. Probiotics are able to positively modify microbiota composition. OBJECTIVE The aim of this review is to report the most important findings regarding the effects of probiotics administration in the most common autoimmune disease and inflammatory immune-mediated diseases. METHODS Literature research was performed in PubMed, Google Scholar, and Medline, as well as in specific journal websites using the keywords: "autoimmunity", "microbiota", and "probiotics". The article selection has been made independently by three authors, and controversies have been solved by a fourth researcher. Only English-language articles were included and preference was given to clinical trials, meta-analysis, and case series. After the review process, 68 articles have been considered. RESULTS Relying on this evidence, many studies have investigated the potential of probiotics in restoring gut eubiosis, thus affecting pathogenesis, clinical manifestations, and course of these pathologies. Even in the light of few and sometimes contradictory studies, physicians should start to consider these preliminary findings when approaching patients suffering from autoimmune disease. After an accurate case-by-case evaluation of potential candidates, probiotics might be introduced besides the standard therapeutic plan as supportive measures.
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Affiliation(s)
- Andrea Piccioni
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Sara Cicchinelli
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Federico Valletta
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Giulio De Luca
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Yaroslava Longhitano
- Department of Internal Medicine, University of Genoa - Dietetics and Clinical Nutrition Unit, IRCCS Polyclinic Hospital San Martino, 16132 Genoa, Italy
| | - Marcello Candelli
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Veronica Ojetti
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Francesco Sardeo
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Simone Navarra
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Marcello Covino
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Francesco Franceschi
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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Adams SH. Historical analysis of inverse correlation between soil-transmitted helminthiasis and pancreatic cancer. Proc AMIA Symp 2020; 34:250-259. [PMID: 33678958 PMCID: PMC7901387 DOI: 10.1080/08998280.2020.1836712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 09/30/2020] [Accepted: 10/01/2020] [Indexed: 12/09/2022] Open
Abstract
In this descriptive epidemiological study, the soil-transmitted helminth (STH) burden and pancreatic cancer (PC) mortality rates of different countries and peoples are compared to demonstrate an inverse correlation. Formerly ubiquitous helminth infection possibly played a significant role in defending the human host against PC until the advancement of modern hygiene, with helminth eradication in recent times in developed countries and urban centers. It is posited that a high rate of infection by STH in developing countries and rural areas protects the human host from the development of PC, possibly by immune modulation. This hypothesis is used to explain increased PC rates in minority groups in the United States who had decreased helminth exposure in the late 20th century.
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Affiliation(s)
- Steven H Adams
- College of Medicine, State University of New York Upstate Medical University, Syracuse, New York
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Beyond Just Bacteria: Functional Biomes in the Gut Ecosystem Including Virome, Mycobiome, Archaeome and Helminths. Microorganisms 2020; 8:microorganisms8040483. [PMID: 32231141 PMCID: PMC7232386 DOI: 10.3390/microorganisms8040483] [Citation(s) in RCA: 88] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 03/26/2020] [Accepted: 03/26/2020] [Indexed: 12/20/2022] Open
Abstract
Gut microbiota refers to a complex network of microbes, which exerts a marked influence on the host’s health. It is composed of bacteria, fungi, viruses, and helminths. Bacteria, or collectively, the bacteriome, comprises a significant proportion of the well-characterized microbiome. However, the other communities referred to as ‘dark matter’ of microbiomes such as viruses (virome), fungi (mycobiome), archaea (archaeome), and helminths have not been completely elucidated. Development of new and improved metagenomics methods has allowed the identification of complete genomes from the genetic material in the human gut, opening new perspectives on the understanding of the gut microbiome composition, their importance, and potential clinical applications. Here, we review the recent evidence on the viruses, fungi, archaea, and helminths found in the mammalian gut, detailing their interactions with the resident bacterial microbiota and the host, to explore the potential impact of the microbiome on host’s health. The role of fecal virome transplantations, pre-, pro-, and syn-biotic interventions in modulating the microbiome and their related concerns are also discussed.
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Arroyo-López C. Helminth therapy for autism under gut-brain axis- hypothesis. Med Hypotheses 2019; 125:110-118. [PMID: 30902137 DOI: 10.1016/j.mehy.2019.02.042] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 02/18/2019] [Indexed: 12/20/2022]
Abstract
Autism is a neurodevelopmental disease included within Autism Syndrome Disorder (ASD) spectrum. ASD has been linked to a series of genes that play a role in immune response function and patients with autism, commonly suffer from immune-related comorbidities. Despite the complex pathophysiology of autism, Gut-brain axis is gaining strength in the understanding of several neurological disorders. In addition, recent publications have shown the correlation between immune dysfunctions, gut microbiota and brain with the behavioral alterations and comorbid symptoms found in autism. Gut-brain axis acts as the "second brain", in a communication network established between neural, endocrine and the immunological systems. On the other hand, Hygiene Hypothesis suggests that the increase in the incidence of autoimmune diseases in the modern world can be attributed to the decrease of exposure to infectious agents, as parasitic nematodes. Helminths induce modulatory and protective effects against several inflammatory disorders, maintaining gastrointestinal homeostasis and modulating brain functions. Helminthic therapy has been previously performed in diseases such as ulcerative colitis, Crohn's disease, diabetes, multiple sclerosis, asthma, rheumatoid arthritis, and food allergies. Considering gut-brain axis, Hygiene Hypothesis, and the modulatory effects of helminths I hypothesized that a treatment with Trichuris suis soluble products represents a feasible holistic treatment for autism, and the key for the development of novel treatments. Preclinical studies are required to test this hypothesis.
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Affiliation(s)
- Celia Arroyo-López
- Department of Pathology and Laboratory Medicine, UC Davis School of Medicine; Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern California, United States.
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Nath A, Haktanirlar G, Varga Á, Molnár MA, Albert K, Galambos I, Koris A, Vatai G. Biological Activities of Lactose-Derived Prebiotics and Symbiotic with Probiotics on Gastrointestinal System. ACTA ACUST UNITED AC 2018; 54:medicina54020018. [PMID: 30344249 PMCID: PMC6037253 DOI: 10.3390/medicina54020018] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2018] [Revised: 03/23/2018] [Accepted: 04/04/2018] [Indexed: 02/07/2023]
Abstract
Lactose-derived prebiotics provide wide ranges of gastrointestinal comforts. In this review article, the probable biochemical mechanisms through which lactose-derived prebiotics offer positive gastrointestinal health are reported along with the up-to-date results of clinical investigations; this might be the first review article of its kind, to the best of our knowledge. Lactose-derived prebiotics have unique biological and functional values, and they are confirmed as ‘safe’ by the Food and Drug Administration federal agency. Medical practitioners frequently recommend them as therapeutics as a pure form or combined with dairy-based products (yoghurt, milk and infant formulas) or fruit juices. The biological activities of lactose-derived prebiotics are expressed in the presence of gut microflora, mainly probiotics (Lactobacillus spp. in the small intestine and Bifidobacterium spp. in the large intestine). Clinical investigations reveal that galacto-oligosaccharide reduces the risks of several types of diarrhea (traveler’s diarrhea, osmotic diarrhea and Clostridium difficile associated relapsing diarrhea). Lactulose and lactosucrose prevent inflammatory bowel diseases (Crohn’s disease and ulcerative colitis). Lactulose and lactitol reduce the risk of hepatic encephalopathy. Furthermore, lactulose, galacto-oligosaccharide and lactitol prevent constipation in individuals of all ages. It is expected that the present review article will receive great attention from medical practitioners and food technologists.
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Affiliation(s)
- Arijit Nath
- Department of Food Engineering, Faculty of Food Science, Szent István University, Ménesi st 44, H-1118 Budapest, Hungary.
- Soós Ernő Water Technology Research Centre, Faculty of Engineering, University of Pannonia, Zrínyi M. u. 18, H-8800 Nagykanizsa, Hungary.
| | - Gokce Haktanirlar
- Department of Food Engineering, Faculty of Food Science, Szent István University, Ménesi st 44, H-1118 Budapest, Hungary.
| | - Áron Varga
- Department of Food Engineering, Faculty of Food Science, Szent István University, Ménesi st 44, H-1118 Budapest, Hungary.
| | - Máté András Molnár
- Department of Food Engineering, Faculty of Food Science, Szent István University, Ménesi st 44, H-1118 Budapest, Hungary.
| | - Krisztina Albert
- Department of Food Engineering, Faculty of Food Science, Szent István University, Ménesi st 44, H-1118 Budapest, Hungary.
| | - Ildikó Galambos
- Soós Ernő Water Technology Research Centre, Faculty of Engineering, University of Pannonia, Zrínyi M. u. 18, H-8800 Nagykanizsa, Hungary.
| | - András Koris
- Department of Food Engineering, Faculty of Food Science, Szent István University, Ménesi st 44, H-1118 Budapest, Hungary.
| | - Gyula Vatai
- Department of Food Engineering, Faculty of Food Science, Szent István University, Ménesi st 44, H-1118 Budapest, Hungary.
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Salgado VCL, Luiz RR, Boechat N, Schorr BC, Leão IS, Nunes T, Zaltman C. Crohn's disease environmental factors in the developing world: A case-control study in a statewide catchment area in Brazil. World J Gastroenterol 2017; 23:5549-5556. [PMID: 28852314 PMCID: PMC5558118 DOI: 10.3748/wjg.v23.i30.5549] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Revised: 05/10/2017] [Accepted: 07/04/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To identify environmental risk factors associated with the development of Crohn's disease (CD) in order to re-assess the hygiene hypothesis. METHODS A hospital-based, case-control study was carried out with CD patients (n = 145) and controls (n = 163) representing a socioeconomically diverse statewide catchment area in Brazil. Controls were recruited from caregivers of patients seen in different outpatient clinics at the same hospital. A multi-item survey with 94 questions regarding family history of CD, perinatal and childhood circumstances, living conditions, tobacco use and familial socioeconomic status was carried out by interviewers. RESULTS On the univariate analysis, predictive variables for CD included being male, under age of 40, a high education level, urban dweller, smaller family size, exposure to enteric pathogens and user of treated water (P < 0.005). On the multivariate analysis, variables significantly associated with CD were male gender (OR = 2.09), under age 40 (OR = 3.10), white (OR = 2.32), from a small family in childhood (OR = 2.34) and adulthood (OR = 3.02), absence of viral infections in childhood (OR = 2.23), exposure to enteric pathogens (OR = 2.41), having had an appendectomy (OR = 2.47) and prior or current smoker (OR = 2.83/1.12). CONCLUSION Most variables supporting the "hygiene hypothesis" are associated with the development of CD but are not independent predictors of the diagnosis.
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Park YH, Jeong MS, Ha KT, Yu HS, Jang SB. Structural characterization of As-MIF and hJAB1 during the inhibition of cell-cycle regulation. BMB Rep 2017; 50:269-274. [PMID: 28366190 PMCID: PMC5458677 DOI: 10.5483/bmbrep.2017.50.5.201] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Indexed: 12/03/2022] Open
Abstract
The biological activities of macrophage migration inhibitory factor (MIF) might be mediated through a classical receptor- mediated or non-classical endocytic pathway. JAB1 (C-Jun activation domain-binding protein-1) promotes the degradation of the tumor suppressor, p53, and the cyclin-dependent kinase inhibitor, p27. When MIF and JAB1 are bound to each other in various intracellular sites, MIF inhibits the positive regulatory effects of JAB1 on the activity of AP-1. The intestinal parasite, Anisakis simplex, has an immunomodulatory effect. The molecular mechanism of action of As-MIF and human JAB1 are poorly understood. In this study, As-MIF and hJAB1 were expressed and purified with high solubility. The structure of As-MIF and hJAB1 interaction was modeled by homology modeling based on the structure of Ace-MIF. This study provides evidence indicating that the MIF domain of As-MIF interacts directly with the MPN domain of hJAB1, and four structure-based mutants of As-MIF and hJAB1 disrupt the As-MIF-hJAB1 interaction.
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Affiliation(s)
- Young-Hoon Park
- Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 46241, Korea
| | - Mi Suk Jeong
- Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 46241, Korea
| | - Ki-Tae Ha
- Department of Korean Medical Science, School of Korean Medicine and Korean Medicine Research Centre for Healthy Aging, Pusan National University, Yangsan 50612, Korea
| | - Hak Sun Yu
- Department of Parasitology, School of Medicine, Pusan National University, Yangsan 50612, Korea
| | - Se Bok Jang
- Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 46241, Korea
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8
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El-Henawy AA, Hafez EAR, Nabih N, Shalaby NM, Mashaly M. Anti-Toxoplasma antibodies in Egyptian rheumatoid arthritis patients. Rheumatol Int 2017; 37:785-790. [DOI: 10.1007/s00296-017-3703-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2016] [Accepted: 03/14/2017] [Indexed: 10/19/2022]
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Cooper AJR, Dholakia S, Holland CV, Friend PJ. Helminths in organ transplantation. THE LANCET. INFECTIOUS DISEASES 2017; 17:e166-e176. [PMID: 28233632 DOI: 10.1016/s1473-3099(16)30533-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/10/2016] [Revised: 11/06/2016] [Accepted: 11/15/2016] [Indexed: 12/26/2022]
Abstract
With transplantation becoming an increasingly routine form of treatment for diverse populations, and with international travel becoming ever more accessible and affordable, the danger of transplantation-mediated helminth infections, exacerbated by coincident immunosuppression, must be considered. In this Review, we attempt to catalogue all clinically-relevant helminthiases that have been reported to coincide with transplantation, whether by transplantation-mediated transmission, reactivation of latent infections in an immunosuppressed context, or possible de-novo infection during the immunosuppressed peritransplant period. Helminthiasis has been reported in cases of kidney, liver, bowel, pancreas, heart, lung, and stem-cell transplant, and blood transfusion. For each helminthiasis, known risk factors, symptoms, and suggested options for screening and treatment are given. We conclude that helminths are a small but important and potentially severe source of disease after transplantation, and, with options for diagnosis and treatment, these pathogens warrant greater consideration during organ implantation. The achievement of immunological tolerance using helminth-derived products is also an exciting future prospect.
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Affiliation(s)
- Andrew J R Cooper
- Department of Zoology, School of Natural Sciences, Trinity College, Dublin, Ireland.
| | - Shamik Dholakia
- Nuffield Department of Surgical Sciences and Oxford Transplant Centre, University of Oxford and Oxford University Hospitals NHS Trust, Oxford, UK
| | - Celia V Holland
- Department of Zoology, School of Natural Sciences, Trinity College, Dublin, Ireland
| | - Peter J Friend
- Nuffield Department of Surgical Sciences and Oxford Transplant Centre, University of Oxford and Oxford University Hospitals NHS Trust, Oxford, UK
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Jörg S, Grohme DA, Erzler M, Binsfeld M, Haghikia A, Müller DN, Linker RA, Kleinewietfeld M. Environmental factors in autoimmune diseases and their role in multiple sclerosis. Cell Mol Life Sci 2016; 73:4611-4622. [PMID: 27491297 PMCID: PMC5097114 DOI: 10.1007/s00018-016-2311-1] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Revised: 07/04/2016] [Accepted: 07/18/2016] [Indexed: 12/19/2022]
Abstract
An increase in autoimmune diseases poses a socioeconomic challenge worldwide. Predisposing genetic risk has been identified, yet environmental factors make up a significant part of the risk in disease initiation and propagation. Next to improved hygiene and a gross reduction of infections, changes in dietary habits are one of the most evident Western lifestyle factors potentially associated with the increase in autoimmune diseases. Growing evidence suggests that particularly a typical 'Western diet', rich in saturated fat and salt and related pathologies can have a profound impact on local and systemic immune responses under physiologic and autoimmune conditions such as in multiple sclerosis (MS). In this review, we discuss recent findings on environmental factors influencing autoimmunity with an emphasis on the impact of 'Western diet' on immune homeostasis and gut microbiota in MS.
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Affiliation(s)
- Stefanie Jörg
- University Hospital Erlangen at the Friedrich-Alexander-University (FAU) Erlangen-Nuremberg, Erlangen, Germany
| | - Diana A Grohme
- Translational Immunology, Department of Clinical Pathobiochemistry, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Melanie Erzler
- Translational Immunology, Department of Clinical Pathobiochemistry, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Marilene Binsfeld
- VIB Laboratory of Translational Immunomodulation & Hasselt University, Diepenbeek, Belgium
| | - Aiden Haghikia
- Department of Neurology, Ruhr-University Bochum, Bochum, Germany
| | - Dominik N Müller
- Experimental and Clinical Research Center, An Institutional Cooperation Between the Charité Medical Faculty and the Max-Delbruck Center for Molecular Medicine, Berlin, Germany
| | - Ralf A Linker
- University Hospital Erlangen at the Friedrich-Alexander-University (FAU) Erlangen-Nuremberg, Erlangen, Germany
| | - Markus Kleinewietfeld
- Translational Immunology, Department of Clinical Pathobiochemistry, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany.
- Center for Regenerative Therapies Dresden (CRTD), Dresden, Germany.
- VIB Laboratory of Translational Immunomodulation & Hasselt University, Diepenbeek, Belgium.
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Abstract
Many immune-mediated diseases like inflammatory bowel disease, multiple sclerosis, type 1 diabetes, asthma, and food allergy appeared to have increased in frequency in developed countries in the latter part of the twentieth century. Reports from less developed countries suggest that the "epidemic" of immune-mediated diseases now is spreading into these regions as well. The "hygiene hypothesis" was developed to partly explain this phenomenon. It has been proposed that modern-day sanitary living has altered our exposure to organisms that provided protection from these diseases in the past. Alternations in the composition of our intestinal flora and fauna could play a role. Helminths are a group of worm-like parasitic organisms that have adapted to live in various regions of their hosts. Epidemiological and some clinical data suggest that these organisms can protect people from developing immune-mediated diseases. Animal experimentation has shown that helminths stimulate the production of regulatory cytokines, activate regulatory T cells, and induce regulatory dendritic cells and macrophages. This could be the mechanism by which they protect the host from these diseases. Early clinical studies also suggest that helminths may prove useful for treating immunological diseases. More sophisticated clinical studies are underway, testing live helminth agents as therapeutic agents. Also, a strong effort is ongoing to discover the agents produced by helminths that modulate host immune responses with an eye on developing new, highly effective immune modulatory therapeutic agent.
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Affiliation(s)
- Joel V Weinstock
- Division of Gastroenterology (Box 233), Tufts Medical Center, 800 Washington St., Boston, MA, 02111, USA.
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Fonseca DMD, Hand TW, Han SJ, Gerner MY, Glatman Zaretsky A, Byrd AL, Harrison OJ, Ortiz AM, Quinones M, Trinchieri G, Brenchley JM, Brodsky IE, Germain RN, Randolph GJ, Belkaid Y. Microbiota-Dependent Sequelae of Acute Infection Compromise Tissue-Specific Immunity. Cell 2016; 163:354-66. [PMID: 26451485 DOI: 10.1016/j.cell.2015.08.030] [Citation(s) in RCA: 205] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2015] [Revised: 07/09/2015] [Accepted: 08/11/2015] [Indexed: 02/07/2023]
Abstract
Infections have been proposed as initiating factors for inflammatory disorders; however, identifying associations between defined infectious agents and the initiation of chronic disease has remained elusive. Here, we report that a single acute infection can have dramatic and long-term consequences for tissue-specific immunity. Following clearance of Yersinia pseudotuberculosis, sustained inflammation and associated lymphatic leakage in the mesenteric adipose tissue deviates migratory dendritic cells to the adipose compartment, thereby preventing their accumulation in the mesenteric lymph node. As a consequence, canonical mucosal immune functions, including tolerance and protective immunity, are persistently compromised. Post-resolution of infection, signals derived from the microbiota maintain inflammatory mesentery remodeling and consequently, transient ablation of the microbiota restores mucosal immunity. Our results indicate that persistent disruption of communication between tissues and the immune system following clearance of an acute infection represents an inflection point beyond which tissue homeostasis and immunity is compromised for the long-term. VIDEO ABSTRACT.
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Affiliation(s)
- Denise Morais da Fonseca
- Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH), Bethesda, MD 20892, USA; Immunity at Barrier Sites Initiative, NIAID/NIH, Bethesda, MD 20892, USA; Department of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, 14049-900, Brazil
| | - Timothy W Hand
- Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH), Bethesda, MD 20892, USA; Immunity at Barrier Sites Initiative, NIAID/NIH, Bethesda, MD 20892, USA
| | - Seong-Ji Han
- Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH), Bethesda, MD 20892, USA; Immunity at Barrier Sites Initiative, NIAID/NIH, Bethesda, MD 20892, USA
| | - Michael Y Gerner
- Lymphocyte Biology Section, Laboratory of Systems Biology, NIAID/NIH, Bethesda, MD 20892, USA
| | - Arielle Glatman Zaretsky
- Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH), Bethesda, MD 20892, USA; Immunity at Barrier Sites Initiative, NIAID/NIH, Bethesda, MD 20892, USA
| | - Allyson L Byrd
- Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH), Bethesda, MD 20892, USA; Immunity at Barrier Sites Initiative, NIAID/NIH, Bethesda, MD 20892, USA; Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA; Department of Bioinformatics, Boston University, Boston, MA 02215, USA
| | - Oliver J Harrison
- Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH), Bethesda, MD 20892, USA; Immunity at Barrier Sites Initiative, NIAID/NIH, Bethesda, MD 20892, USA
| | - Alexandra M Ortiz
- Program in Tissue Immunity and Repair and Immunopathogenesis Section, Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20892, USA
| | - Mariam Quinones
- Bioinformatics and Computational Bioscience Branch, NIAID/NIH, Bethesda, MD 20892, USA
| | - Giorgio Trinchieri
- Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
| | - Jason M Brenchley
- Program in Tissue Immunity and Repair and Immunopathogenesis Section, Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20892, USA
| | - Igor E Brodsky
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Ronald N Germain
- Lymphocyte Biology Section, Laboratory of Systems Biology, NIAID/NIH, Bethesda, MD 20892, USA
| | - Gwendalyn J Randolph
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Yasmine Belkaid
- Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH), Bethesda, MD 20892, USA; Immunity at Barrier Sites Initiative, NIAID/NIH, Bethesda, MD 20892, USA.
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Beales DL. Biome depletion in conjunction with evolutionary mismatches could play a role in the etiology of neurofibromatosis 1. Med Hypotheses 2015; 84:305-14. [PMID: 25665856 DOI: 10.1016/j.mehy.2015.01.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Revised: 12/31/2014] [Accepted: 01/12/2015] [Indexed: 12/22/2022]
Abstract
Neurofibromatosis 1 (NF1) arises de novo in a striking 30-50% of cases, pointing toward an environmental etiology, though none has been clearly identified. The Biome Depletion Theory posits that the absence of mutualistic and commensal organisms within the human body coupled with modern lifestyle alterations may have profoundly deleterious effects, inclusive of immunologic derangement that is thought to result in allergy, atopy, and numerous autoimmune diseases. Biome depletion has been implicated as a factor in the etiology of both multiple sclerosis and autism spectrum disorders; biome reconstitution, i.e. replenishment of the biome with certain keynote species, is being used in the treatment of these and other autoimmune states. Neurofibromatosis 1 has been associated with allergy, various autoimmune states, multiple sclerosis, and autism. Recent research has posited that NF1, multiple sclerosis and autism may all arise from disturbances in the neural crest during gestation. This paper hypothesizes that there is indirect evidence that a highly inflammatory uterine state may precipitate epigenetic changes in vulnerable NF-related genes in the course of fetal development. The etiology of NF1 may lie in the absence of immunomodulation by commensal and mutualistic species once ubiquitously present in the environment, as well as through adoption of a modern lifestyle that contributes to chronic inflammation. Replenishment of helminths and other missing organisms to the human biome prior to conception as well as addressing nutritional status, psychological stress, and environmental exposures may prevent the development of NF1.
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Affiliation(s)
- Donna L Beales
- Lowell General Hospital, Medical Library, 295 Varnum Avenue, Lowell, MA 01854, United States.
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Fakhoury M, Negrulj R, Mooranian A, Al-Salami H. Inflammatory bowel disease: clinical aspects and treatments. J Inflamm Res 2014; 7:113-20. [PMID: 25075198 PMCID: PMC4106026 DOI: 10.2147/jir.s65979] [Citation(s) in RCA: 327] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel disease (IBD) is defined as a chronic intestinal inflammation that results from host-microbial interactions in a genetically susceptible individual. IBDs are a group of autoimmune diseases that are characterized by inflammation of both the small and large intestine, in which elements of the digestive system are attacked by the body’s own immune system. This inflammatory condition encompasses two major forms, known as Crohn’s disease and ulcerative colitis. Patients affected by these diseases experience abdominal symptoms, including diarrhea, abdominal pain, bloody stools, and vomiting. Moreover, defects in intestinal epithelial barrier function have been observed in a number of patients affected by IBD. In this review, we first describe the types and symptoms of IBD and investigate the role that the epithelial barrier plays in the pathophysiology of IBD as well as the major cytokines involved. We then discuss steps used to diagnose this disease and the treatment options available, and finally provide an overview of the recent research that aims to develop new therapies for such chronic disorders.
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Affiliation(s)
- Marc Fakhoury
- Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical engineering and Artificial Cells and Organs Research Center, Faculty of Medicine, McGill University, Montreal, QC, Canada
| | - Rebecca Negrulj
- Biotechnology and Drug Development Research Laboratory, Curtin Health Innovation Research Institute, Biosciences Research Precinct, School of Pharmacy, Curtin University, Perth, WA, Australia
| | - Armin Mooranian
- Biotechnology and Drug Development Research Laboratory, Curtin Health Innovation Research Institute, Biosciences Research Precinct, School of Pharmacy, Curtin University, Perth, WA, Australia
| | - Hani Al-Salami
- Biotechnology and Drug Development Research Laboratory, Curtin Health Innovation Research Institute, Biosciences Research Precinct, School of Pharmacy, Curtin University, Perth, WA, Australia
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15
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Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell 2014; 157:121-41. [PMID: 24679531 DOI: 10.1016/j.cell.2014.03.011] [Citation(s) in RCA: 3359] [Impact Index Per Article: 305.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2013] [Revised: 03/10/2014] [Accepted: 03/11/2014] [Indexed: 02/06/2023]
Abstract
The microbiota plays a fundamental role on the induction, training, and function of the host immune system. In return, the immune system has largely evolved as a means to maintain the symbiotic relationship of the host with these highly diverse and evolving microbes. When operating optimally, this immune system-microbiota alliance allows the induction of protective responses to pathogens and the maintenance of regulatory pathways involved in the maintenance of tolerance to innocuous antigens. However, in high-income countries, overuse of antibiotics, changes in diet, and elimination of constitutive partners, such as nematodes, may have selected for a microbiota that lack the resilience and diversity required to establish balanced immune responses. This phenomenon is proposed to account for some of the dramatic rise in autoimmune and inflammatory disorders in parts of the world where our symbiotic relationship with the microbiota has been the most affected.
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Affiliation(s)
- Yasmine Belkaid
- Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
| | - Timothy W Hand
- Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA
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Abstract
Current immunosuppression regimens for solid-organ transplantation have shown disappointing efficacy in the prevention of chronic allograft rejection and carry unacceptable risks including toxicity, neoplasia, and life-threatening infection. Achievement of immunological tolerance (long-term antigen unresponsiveness in an immunocompetent host) presents the exciting prospect of freedom from immunosuppression for transplant recipients. It is now 60 years since the first demonstration of immunological tolerance in animal models of transplantation, but translation into routine clinical practice remains elusive. Helminth parasites may provide novel strategies toward achieving this goal. Helminths are remarkably successful parasites: they currently infect more than one quarter of the world’s population. It is now well established that the parasites’ success is the result of active immunomodulation of their hosts’ immune response. Although this primarily secures ongoing survival of the parasites, helminth-induced immunomodulation can also have a number of benefits for the host. Significant reductions in the prevalence of allergy and autoimmune conditions among helminth-infected populations are well recognized and there is now a significant body of evidence to suggest that harmful immune responses to alloantigens may be abrogated as well. Here, we review all existing studies of helminth infection and transplantation, explore the mechanisms involved, and discuss possible avenues for future translation to clinical practice.
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Abstract
INTRODUCTION Clinical management in inflammatory bowel disease (IBD) is constantly changing. Although improvement in symptoms is of paramount importance, using this as the only surrogate marker of disease activity might underestimate disease burden. SOURCES OF DATA New data from randomized clinical trials are now available. Treatment paradigms are constantly changing leading to an evolution in the therapeutic approach in routine IBD practice. AREAS OF AGREEMENT Patients with an aggressive disease phenotype should be identified at the onset and treated more intensely in order to achieve long-lasting mucosal remission. AREAS OF CONTROVERSY Patients who have mild and indolent disease need to be identified and not over treated. GROWING POINTS The primary endpoint in IBD management should ideally be mucosal healing. Ample data are now available that correlates mucosal healing with surgical-free outcomes with minimal intestinal damage and patient disability. However, the exact degree of mucosal healing that will lead to improved long-term remission, decreased hospital and surgical rates remains unknown. AREAS TIMELY FOR DEVELOPING RESEARCH Clinical translational work is needed to identify novel pathways in IBD pathogenesis that sub-select patients who would benefit by specific-cytokine pathway modulation.
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Affiliation(s)
- G W Moran
- Inflammatory Bowel Disease Clinic, University of Calgary, Calgary, AB, Canada
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Sandborn WJ, Elliott DE, Weinstock J, Summers RW, Landry-Wheeler A, Silver N, Harnett MD, Hanauer SB. Randomised clinical trial: the safety and tolerability of Trichuris suis ova in patients with Crohn's disease. Aliment Pharmacol Ther 2013; 38:255-63. [PMID: 23730956 DOI: 10.1111/apt.12366] [Citation(s) in RCA: 85] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2013] [Revised: 04/29/2013] [Accepted: 05/14/2013] [Indexed: 12/26/2022]
Abstract
BACKGROUND Recent evidence suggests that embryonated eggs of the porcine whipworm Trichuris suis ova (TSO) may be an effective treatment for inflammatory bowel disease (IBD). AIM To assess the safety and tolerability of TSO following a single dose in patients with Crohn's disease. METHODS This was a sequential dose-escalation (500, 2500 and 7500 viable embryonated TSO), randomised, double-blind, placebo-controlled study to evaluate the safety of a single dose of oral suspension TSO in patients with Crohn's disease. Twelve patients were randomised into each of three cohorts. Patients were assessed 1, 3, 5, 7, 9, 11 and 14 days following dosing (via a telephone call and diary symptom collection through 14 days postdose) for adverse events, changes to concomitant medications and gastrointestinal (GI) signs and symptoms. Patients were again assessed at Months 1, 2 and 6. RESULTS Eighteen males and 18 females were enrolled, ages 20 to 54 years. All patients were dosed and completed the initial 2-month follow-up period (five patients did not attend their 6-month study visit). GI disorders were reported with the highest frequency; 7 (25.9%) TSO-treated patients and 3 (33.3%) placebo-treated patients. No dose-dependent relationship was observed, with 3 (33.3%) placebo, 4 (44.4%) TSO 500, 0 (0.0%) TSO 2500 and 3 (33.3%) TSO 7500 patients experiencing at least one GI event, and no clinically meaningful changes in GI signs and symptoms. CONCLUSIONS A single dose of Trichuris suis ova up to 7500 ova was well tolerated and did not result in short- or long-term treatment-related side effects. Clinicaltrials.gov NCT01576461.
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Affiliation(s)
- W J Sandborn
- Division of Gastroenterology, University of California San Diego, La Jolla, CA 92093-0956, USA.
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Blum AM, Hang L, Setiawan T, Urban JP, Stoyanoff KM, Leung J, Weinstock JV. Heligmosomoides polygyrus bakeri induces tolerogenic dendritic cells that block colitis and prevent antigen-specific gut T cell responses. THE JOURNAL OF IMMUNOLOGY 2012; 189:2512-20. [PMID: 22844110 DOI: 10.4049/jimmunol.1102892] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Immunological diseases such as inflammatory bowel disease (IBD) are infrequent in less developed countries, possibly because helminths provide protection by modulating host immunity. In IBD murine models, the helminth Heligmosomoides polygyrus bakeri prevents colitis. It was determined whether H. polygyrus bakeri mediated IBD protection by altering dendritic cell (DC) function. We used a Rag IBD model where animals were reconstituted with IL10⁻/⁻ T cells, making them susceptible to IBD and with OVA Ag-responsive OT2 T cells, allowing study of a gut antigenic response. Intestinal DC from H. polygyrus bakeri-infected Rag mice added to lamina propria mononuclear cells (LPMC) isolated from colitic animals blocked OVA IFN-γ/IL-17 responses in vitro through direct contact with the inflammatory LPMC. DC from uninfected Rag mice displayed no regulatory activity. Transfer of DC from H. polygyrus bakeri-infected mice into Rag mice reconstituted with IL10⁻/⁻ T cells protected animals from IBD, and LPMC from these mice lost OVA responsiveness. After DC transfer, OT2 T cells populated the intestines normally. However, the OT2 T cells were rendered Ag nonresponsive through regulatory action of LPMC non-T cells. The process of regulation appeared to be regulatory T cell independent. Thus, H. polygyrus bakeri modulates intestinal DC function, rendering them tolerogenic. This appears to be an important mechanism through which H. polygyrus bakeri suppresses colitis. IFN-γ and IL-17 are colitogenic. The capacity of these DC to block a gut Ag-specific IFN-γ/IL-17 T cell response also is significant.
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Affiliation(s)
- Arthur M Blum
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, Tufts Medical Center, Boston, MA 02111, USA
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References. Parasitology 2012. [DOI: 10.1002/9781119968986.refs] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Henneberg M, Saniotis A. How can evolutionary medicine inform future personalized medicine? Per Med 2012; 9:171-173. [PMID: 29758821 DOI: 10.2217/pme.11.99] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Affiliation(s)
- Maciej Henneberg
- School of Medical Sciences, The University of Adelaide, Adelaide, Australia and Center for Evolutionary Medicine, University of Zürich, Switzerland
| | - Arthur Saniotis
- School of Medical Sciences, The University of Adelaide, Adelaide, Australia and Center for Evolutionary Medicine, University of Zürich, Switzerland.
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Parasites or cohabitants: cruel omnipresent usurpers or creative "éminences grises"? J Parasitol Res 2011; 2011:214174. [PMID: 21785696 PMCID: PMC3140032 DOI: 10.1155/2011/214174] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2011] [Accepted: 04/06/2011] [Indexed: 12/31/2022] Open
Abstract
This paper presents many types of interplays between parasites and the host, showing the history of parasites, the effects of parasites on the outcome of wars, invasions, migrations, and on the development of numerous regions of the globe, and the impact of parasitic diseases on the society and on the course of human evolution. It also emphasizes the pressing need to change the look at the parasitism phenomenon, proposing that the term “cohabitant” is more accurate than parasite, because every living being, from bacteria to mammals, is a consortium of living beings in the pangenome. Even the term parasitology should be replaced by cohabitology because there is no parasite alone and host alone: both together compose a new adaptive system: the parasitized-host or the cohabitant-cohabited being. It also suggests switching the old paradigm based on attrition and destruction, to a new one founded on adaptation and living together.
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Bodammer P, Waitz G, Loebermann M, Holtfreter MC, Maletzki C, Krueger MR, Nizze H, Emmrich J, Reisinger EC. Schistosoma mansoni infection but not egg antigen promotes recovery from colitis in outbred NMRI mice. Dig Dis Sci 2011; 56:70-8. [PMID: 20428947 DOI: 10.1007/s10620-010-1237-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2009] [Accepted: 04/06/2010] [Indexed: 12/12/2022]
Abstract
BACKGROUND The ability of intestinal helminths to manipulate the immune system of their host towards a Th2 response has been proposed to modulate auto-immune and allergic diseases. AIMS This initial study investigated the anti-inflammatory potential of S. mansoni and soluble egg antigen (SEA) in a murine model of colitis. METHODS Colitis was induced in female NMRI mice by 5% dextran sulfate sodium (DSS) for 7 days, either 9 weeks post-infection with S. mansoni or during treatment with SEA. In addition to clinical signs of colitis, colon histology, immunohistochemistry, and flow cytometry of leukocytes were performed. Colon cytokines were measured using a quantitative real-time technique. RESULTS Infection with cercariae of S. mansoni attenuated DSS-induced colitis. Clinical symptoms such as weight loss and shortening of colon length were significantly prevented. Histological scores and cell infiltration were affected and expression of pro-inflammatory cytokines in the colons of infected DSS colitis mice was reduced. In contrast, application of SEA failed to improve colitis, even though some findings like earlier manifestation of inflammation and local induction of Th2 cytokines were similar to the effects of cercarial infection. CONCLUSIONS The results presented here suggest that SEA treatment could not protect mice from acute colitis. However, both infection with S. mansoni and injection of SEA affect mucosal immune responses.
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Affiliation(s)
- Peggy Bodammer
- Division of Tropical Medicine and Infectious Diseases, Department of Internal Medicine, University of Rostock, Rostock, Germany.
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Hang L, Setiawan T, Blum AM, Urban J, Stoyanoff K, Arihiro S, Reinecker HC, Weinstock JV. Heligmosomoides polygyrus infection can inhibit colitis through direct interaction with innate immunity. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2010; 185:3184-9. [PMID: 20702728 PMCID: PMC2948844 DOI: 10.4049/jimmunol.1000941] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Less developed countries have a low incidence of immunological diseases like inflammatory bowel disease (IBD), perhaps prevented by the high prevalence of helminth infections in their populations. In the Rag IL-10(-/-) T cell transfer model of colitis, Heligmosomoides polygyrus, an intestinal helminth, prevents and reverses intestinal inflammation. This model of colitis was used to explore the importance of innate immunity in H. polygyrus protection from IBD. Rag mice briefly exposed to H. polygyrus before reconstitution with IL-10(-/-) colitogenic T cells are protected from colitis. Exposure to H. polygyrus before introduction of IL-10(-/-) and OT2 T cells reduced the capacity of the intestinal mucosa to make IFN-gamma and IL-17 after either anti-CD3 mAb or OVA stimulation. This depressed cytokine response was evident even in the absence of colitis, suggesting that the downmodulation in proinflammatory cytokine secretion was not just secondary to improvement in intestinal inflammation. Following H. polygyrus infection, dendritic cells (DCs) from the lamina propria of Rag mice displayed decreased expression of CD80 and CD86, and heightened expression of plasmacytoid dendritic cell Ag-1 and CD40. They were also less responsive to lamina proprias, producing less IL-12p40 and IL-10. Also diminished was their capacity to present OVA to OT2 T cells. These experiments infer that H. polygyrus does not require direct interactions with T or B cells to render animals resistant to colitis. DCs have an important role in driving both murine and human IBD. Data suggest that phenotypic alternations in mucosal DC function are part of the regulatory process.
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Affiliation(s)
- Long Hang
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, Tufts Medical Center, Boston, MA 02111, USA
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Bruschi F, Chiumiento L, Prete GD. Immunodulation and Helminths: Towards New Strategies for Treatment of Immune-Mediated Diseases? DETECTION OF BACTERIA, VIRUSES, PARASITES AND FUNGI 2010. [DOI: 10.1007/978-90-481-8544-3_15] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Prieto-Lafuente L, Gregory WF, Allen JE, Maizels RM. MIF homologues from a filarial nematode parasite synergize with IL-4 to induce alternative activation of host macrophages. J Leukoc Biol 2009; 85:844-54. [PMID: 19179453 PMCID: PMC2691607 DOI: 10.1189/jlb.0808459] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2008] [Revised: 12/19/2008] [Accepted: 12/22/2008] [Indexed: 12/18/2022] Open
Abstract
Macrophage migration inhibitory factor (MIF) is a highly conserved cytokine considered to exert wide-ranging, proinflammatory effects on the immune system. Recently, members of this gene family have been discovered in a number of invertebrate species, including parasitic helminths. However, chronic helminth infections are typically associated with a Th2-dominated, counter-inflammatory phenotype, in which alternatively activated macrophages (AAMs) are prominent. To resolve this apparent paradox, we have analyzed the activity of two helminth MIF homologues from the filarial nematode Brugia malayi, in comparison with the canonical MIF from the mouse. We report that murine MIF (mMIF) and Brugia MIF proteins induce broadly similar effects on bone marrow-derived mouse macrophages, eliciting a measured release of proinflammatory cytokines. In parallel, MIF was found to induce up-regulation of IL-4R on macrophages, which when treated in vitro with MIF in combination with IL-4, expressed markers of alternative activation [arginase, resistin-like molecule alpha (RELM-alpha) or found in inflammatory zone 1, Ym-1, murine macrophage mannose receptor] and differentiated into functional AAMs with in vitro-suppressive ability. Consistent with this finding, repeated in vivo administration of Brugia MIF induced expression of alternative macrophage activation markers. As mMIF did not induce RELM-alpha or Ym-1 in vivo, alternative activation may require components of the adaptive immune response to Brugia MIF, such as the production of IL-4. Hence, MIF may accentuate macrophage activation according to the polarity of the environment, thus promoting AAM differentiation in the presence of IL-4-inducing parasitic helminths.
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Affiliation(s)
- Lidia Prieto-Lafuente
- Institute of Immunology and Infection Research, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK
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Ruyssers NE, De Winter BY, De Man JG, Loukas A, Pearson MS, Weinstock JV, Van den Bossche RM, Martinet W, Pelckmans PA, Moreels TG. Therapeutic potential of helminth soluble proteins in TNBS-induced colitis in mice. Inflamm Bowel Dis 2009; 15:491-500. [PMID: 19023900 DOI: 10.1002/ibd.20787] [Citation(s) in RCA: 133] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The hygiene hypothesis suggests an inverse relationship between the incidence of parasitic infections and chronic inflammatory bowel diseases (IBD). We investigated the therapeutic potential of Schistosoma mansoni and Ancylostoma caninum soluble proteins on experimental colitis in mice. METHODS Colitis was induced by intrarectal administration of 10 mg trinitrobenzene sulfonic acid (TNBS) in 30% ethanol. Six hours after TNBS injection, mice were treated intraperitoneally with helminth proteins. Three days later, colonic inflammation was scored based on 5 inflammatory parameters: clinical disease activity, macroscopic and microscopic inflammation score, extent of inflammation, and myeloperoxidase (MPO) activity. To determine immunological pathways induced by S. mansoni proteins we measured cytokine profiles of T-lymphocytes from colon, mesenteric lymph nodes (MLN), and spleen by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS Control mice showed no signs of inflammation, whereas all inflammatory parameters were significantly increased in mice with colitis. Treatment of mice with colitis with S. mansoni or A. caninum proteins decreased the macroscopic inflammation score, extent of inflammation, and MPO activity. Immunologically, induction of colitis significantly increased expression of IFN-gamma mRNA in the inflamed colon. Treatment with S. mansoni proteins caused a decrease of proinflammatory cytokines (IFN-gamma, IL-17) in colon and MLN, whereas the production of regulatory cytokines (IL-10, TGF-beta) increased significantly in colon tissue. CONCLUSIONS Treatment with proteins of S. mansoni and A. caninum ameliorated TNBS-induced colitis in mice. S. mansoni proteins increased mRNA expression of regulatory cytokines while suppressing expression of proinflammatory cytokines. Therefore, we suggest a therapeutic potential for helminth proteins in the treatment of IBD.
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Affiliation(s)
- Nathalie E Ruyssers
- Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium
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Salinas-Carmona MC, de la Cruz-Galicia G, Pérez-Rivera I, Solís-Soto JM, Segoviano-Ramirez JC, Vázquez AV, Garza MA. Spontaneous arthritis in MRL/lpr mice is aggravated by Staphylococcus aureus and ameliorated by Nippostrongylus brasiliensis infections. Autoimmunity 2009; 42:25-32. [PMID: 18608175 DOI: 10.1080/08916930802228290] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Rheumatoid arthritis is an autoimmune disease that affects human beings worldwide. Infections have been associated to autoimmune diseases because their ability to induce a dominant cytokine response. Joint inflammation has been related to Th1 response because they induce high expression of proinflammatory cytokines TNF-alpha, IL-1, IFN-gamma. MRL/lpr mice spontaneously develop an autoimmune disease affecting joints, kidneys, etc. We compared incidence and severity of arthritis, antibody response, cytokine production, in mice infected with bacteria or helminthes in the Murphy Roths Large (MRL)lpr mice. Infections with helminthes Heligmosomoides polygyrus, Nippostrongylus brasiliensis or bacteria Nocardia brasiliensis and Staphylococcus aureus were studied. IL-4, IFN-gamma and IgG1, IgG2a antibody productions were determined. IFN-gamma was increased in all groups, the highest production was observed after bacterial infection; IL-4 production was higher after helminthes infection. IgG1 sera levels were increased in the helminthes infected group. IgG2a sera concentration was stimulated by bacterial infection. The histopathology showed that 100% of bacterial infected mice developed arthritis and severe tissue damage such as cartilage erosion and bone destruction. Animals infected with parasites showed a decreased incidence and severity of arthritis. Severity of tissue damage in joints is correlated with increased numbers of lymphocytes and macrophages immunoreactive to proinflammatory cytokines.
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de Silva H, de Silva N, de Silva A, Jewell D. Emergence of inflammatory bowel disease ‘beyond the West’: do prosperity and improved hygiene have a role? Trans R Soc Trop Med Hyg 2008; 102:857-60. [DOI: 10.1016/j.trstmh.2008.03.016] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2007] [Revised: 03/18/2008] [Accepted: 03/18/2008] [Indexed: 10/22/2022] Open
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Nesse RM, Stearns SC. The great opportunity: Evolutionary applications to medicine and public health. Evol Appl 2008; 1:28-48. [PMID: 25567489 PMCID: PMC3352398 DOI: 10.1111/j.1752-4571.2007.00006.x] [Citation(s) in RCA: 121] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2007] [Accepted: 11/27/2007] [Indexed: 02/06/2023] Open
Abstract
Evolutionary biology is an essential basic science for medicine, but few doctors and medical researchers are familiar with its most relevant principles. Most medical schools have geneticists who understand evolution, but few have even one evolutionary biologist to suggest other possible applications. The canyon between evolutionary biology and medicine is wide. The question is whether they offer each other enough to make bridge building worthwhile. What benefits could be expected if evolution were brought fully to bear on the problems of medicine? How would studying medical problems advance evolutionary research? Do doctors need to learn evolution, or is it valuable mainly for researchers? What practical steps will promote the application of evolutionary biology in the areas of medicine where it offers the most? To address these questions, we review current and potential applications of evolutionary biology to medicine and public health. Some evolutionary technologies, such as population genetics, serial transfer production of live vaccines, and phylogenetic analysis, have been widely applied. Other areas, such as infectious disease and aging research, illustrate the dramatic recent progress made possible by evolutionary insights. In still other areas, such as epidemiology, psychiatry, and understanding the regulation of bodily defenses, applying evolutionary principles remains an open opportunity. In addition to the utility of specific applications, an evolutionary perspective fundamentally challenges the prevalent but fundamentally incorrect metaphor of the body as a machine designed by an engineer. Bodies are vulnerable to disease - and remarkably resilient - precisely because they are not machines built from a plan. They are, instead, bundles of compromises shaped by natural selection in small increments to maximize reproduction, not health. Understanding the body as a product of natural selection, not design, offers new research questions and a framework for making medical education more coherent. We conclude with recommendations for actions that would better connect evolutionary biology and medicine in ways that will benefit public health. It is our hope that faculty and students will send this article to their undergraduate and medical school Deans, and that this will initiate discussions about the gap, the great opportunity, and action plans to bring the full power of evolutionary biology to bear on human health problems.
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Trichinella spiralis: modulation of experimental autoimmune encephalomyelitis in DA rats. Exp Parasitol 2008; 118:641-7. [PMID: 18226814 DOI: 10.1016/j.exppara.2007.12.003] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2007] [Revised: 10/26/2007] [Accepted: 12/10/2007] [Indexed: 11/23/2022]
Abstract
Helminth infection has a potent systemic immunomodulatory effect on the host immune response, which also affects the development of autoimmune diseases. We investigated the dose-dependent influence of Trichinella spiralis infection on experimental autoimmune encephalomyelitis (EAE). Our model of concomitant T. spiralis infection and EAE demonstrates that established infection of Dark Agouti (DA) rats with the parasite causes amelioration of the clinical course of induced EAE in a dose-dependent way. Infection with T. spiralis L1 stage muscle larvae (TSL1) reduced the severity of the autoimmune disease as judged by lower maximal clinical score, cumulative index, duration of illness and degree of mononuclear cell infiltration in T. spiralis infected animals compared to control, EAE-induced group. This study provides a valuable model of worm infection to investigate helminth-induced regulatory mechanisms for optimal benefit to the host.
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Ruyssers NE, De Winter BY, De Man JG, Loukas A, Herman AG, Pelckmans PA, Moreels TG. Worms and the treatment of inflammatory bowel disease: are molecules the answer? Clin Dev Immunol 2008; 2008:567314. [PMID: 18509490 PMCID: PMC2396220 DOI: 10.1155/2008/567314] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2008] [Accepted: 04/21/2008] [Indexed: 02/06/2023]
Abstract
The lack of exposure to helminth infections, as a result of improved living standards and medical conditions, may have contributed to the increased incidence of IBD in the developed world. Epidemiological, experimental, and clinical data sustain the idea that helminths could provide protection against IBD. Studies investigating the underlying mechanisms by which helminths might induce such protection have revealed the importance of regulatory pathways, for example, regulatory T-cells. Further investigation on how helminths influence both innate and adaptive immune reactions will shed more light on the complex pathways used by helminths to regulate the hosts immune system. Although therapy with living helminths appears to be effective in several immunological diseases, the disadvantages of a treatment based on living parasites are explicit. Therefore, the identification and characterization of helminth-derived immunomodulatory molecules that contribute to the protective effect could lead to new therapeutic approaches in IBD and other immune diseases.
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Affiliation(s)
- Nathalie E. Ruyssers
- Laboratory of Experimental Medicine and Pediatrics,
Division of Gastroenterology,
University of Antwerp,
2610 Antwerp,
Belgium
| | - Benedicte Y. De Winter
- Laboratory of Experimental Medicine and Pediatrics,
Division of Gastroenterology,
University of Antwerp,
2610 Antwerp,
Belgium
| | - Joris G. De Man
- Laboratory of Experimental Medicine and Pediatrics,
Division of Gastroenterology,
University of Antwerp,
2610 Antwerp,
Belgium
| | - Alex Loukas
- Division of Infectious Diseases,
Queensland Institute of Medical Research,
Brisbane,
QL 4029,
Australia
| | - Arnold G. Herman
- Laboratory of Pharmacology,
University of Antwerp,
2610 Antwerp,
Belgium
| | - Paul A. Pelckmans
- Laboratory of Experimental Medicine and Pediatrics,
Division of Gastroenterology,
University of Antwerp,
2610 Antwerp,
Belgium
| | - Tom G. Moreels
- Laboratory of Experimental Medicine and Pediatrics,
Division of Gastroenterology,
University of Antwerp,
2610 Antwerp,
Belgium
- Division of Gastroenterology and Hepatology,
University Hospital of Antwerp,
Wilrijkstraat 10,
2650 Edegem,
Belgium
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34
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Abstract
The treatment of inflammatory bowel disease (IBD) is undergoing rapid and profound change. Entirely new approaches are being developed that reflect a greater understanding of how to control the inflammatory process. These began with inflixumab therapy for Crohn's disease. Additional tumor necrosis antibodies will soon be employed, and other biological agents are being investigated. Probiotics, helminth ova therapy, alternative and complementary treatments, leukocytophoresis, and bone-marrow and stem-cell transplantation are additional exciting regimens that are being explored. Although some of these approaches provide marked improvement in these parameters, others are unproven or fraught with adverse effects and complications. Still, control of ulcerative colitis and Crohn's is improving with more changes likely to come.
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Affiliation(s)
- Robert W Summers
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, 4545 JCP, University of Iowa, Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA.
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35
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Olivares D, Gisbert JP, Gamallo C, Maté-Jiménez J. Immunological changes at rectal mucosa in appendectomised subjects and inhabitants of developing countries. GASTROENTEROLOGIA Y HEPATOLOGIA 2007; 30:57-60. [PMID: 17335710 DOI: 10.1157/13099263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
AIM It has been suggested that appendicitis protects against ulcerative colitis. We hypothesize that early poor hygiene protects against ulcerative colitis (UC) and predisposes to appendicitis. Our aim was to elucidate the immunological characteristics of rectal mucosa in two populations protected against UC development: appendectomised subjects and inhabitants of developing countries. METHODS this was an age-matched prospective case-control study. Each consecutive individual case appendectomised (group A) was compared to another control from a developing country (group B) and to a control from the general population (group C). Four biopsies from rectal mucosa were taken from all subjects, two for histological and two for histochemical study; specific antibodies were used for T lymphocytes CD3+, CD4+, CD8+ and B lymphocytes CD20+ populations. RESULTS Mucosa samples of 45 non-smoker healthy subjects were studied, of which 15 were from group A, 15 from group B and 15 from group C. In appendectomised subjects, the proportion of CD8+ cells was higher than in the control group (p<0.001), but similar to that in B group. The proportion of CD3+ and CD20+ cells was significatively lower than in Ecuadorians, but similar to the control group. In Ecuadorians, the proportion of CD3+ and CD8+ cells was significatively higher than in the control group (p<0.001), and were similar to that of CD20+. There were no significant differences in the proportion of CD4+. CONCLUSION Appendectomy and deficient environmental hygiene are associated with an increase of CD8+ T lymphocytes in the rectal mucosa. Moreover, deficient environmental hygiene is associated with an increase of CD3+ and CD8+ lymphocytes. The CD8+ increase is the only common significant alteration in the mucosa of both groups protected against the development of ulcerative colitis, suggesting that the factors causing changes in lamina propria lymphocytes of both groups are different.
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36
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Marshall JK. Finding inflammatory bowel disease genes will not lead to a cure. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2007; 20:643-4. [PMID: 17066154 PMCID: PMC2660791 DOI: 10.1155/2006/814145] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- John K Marshall
- Division of Gastroenterology, McMaster University, Hamilton, Ontario.
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37
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Reddy A, Fried B. The use of Trichuris suis and other helminth therapies to treat Crohn’s disease. Parasitol Res 2007; 100:921-7. [PMID: 17206504 DOI: 10.1007/s00436-006-0416-4] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2006] [Accepted: 11/25/2006] [Indexed: 12/31/2022]
Abstract
Infections with gastrointestinal (GI) nematodes are prevalent worldwide, despite the fact that anti-helminthic medications are regarded as safe, efficient, and widely available globally. In this review, we highlight the potential therapeutic benefits that may be realized through the clinical use of Trichuris suis and other helminths for Crohn's disease (CD). Long-lived helminthic parasites are remarkable in their ability to down-regulate host immunity, protecting themselves from elimination, and also minimize severe pathological host changes. This review summarizes what is known about the underlying mechanisms that may account for the observed patterns in humans treated with helminths for CD. The Th2 arm of the immune system is emphasized as a component of primary importance in the association between the host immune system and GI nematode infections. Although GI nematode infections in humans cause significant morbidity and mortality, the existence and nature of protective mechanisms these helminths may confer remain largely unclear.
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Affiliation(s)
- Aditya Reddy
- Department of Biology, Lafayette College, Easton, PA 18042, USA.
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38
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Lukas M, Bortlik M, Maratka Z. What is the origin of ulcerative colitis? Still more questions than answers. Postgrad Med J 2006; 82:620-5. [PMID: 17068271 PMCID: PMC2653902 DOI: 10.1136/pmj.2006.047035] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2006] [Accepted: 04/22/2006] [Indexed: 01/28/2023]
Abstract
Despite more than a century of existence as a clinical entity, the true origin of ulcerative colitis still remains elusive. Several factors probably contribute to the development of this condition. Recently discovered technologies have clarified the role of bacterial species, which may account for intestinal dysbiosis, as a factor triggering ulcerative colitis. Genetic susceptibility together with abnormal innate immunoreactivity probably comprise the essential prerequisites for the initiation and perpetuation of ulcerative colitis. Although the genetic background has been more clearly recognised in patients with Crohn's disease than in those with ulcerative colitis, some candidate loci associated with ulcerative colitis have also been intensively studied. Additionally, environmental factors may interfere with inherent predispositions to ulcerative colitis, and either suppress or reinforce them. Whatever the origin, the search for the aetiology of ulcerative colitis must have the same goal: the improvement of treatment and the quality of life in patients with ulcerative colitis.
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Affiliation(s)
- Milan Lukas
- Gastroenterology Center, Fourth Medical Department, General Faculty Hospital, First School of Medicine, Charles University, Prague, Czech Republic.
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39
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Alford L. Findings of interest from immunology and psychoneuroimmunology. ACTA ACUST UNITED AC 2006; 12:176-80. [PMID: 16891144 DOI: 10.1016/j.math.2006.06.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2005] [Revised: 02/19/2006] [Accepted: 06/02/2006] [Indexed: 01/15/2023]
Abstract
The biopsychosocial paradigm is now the main model when dealing with most human health disorders. One of the strengths of this model is that it encourages broader thinking when assessing and managing patients. It also encourages broader reading into areas not traditionally associated with manual therapy. Immunology and neuroscience are amongst the fastest growing medical sciences. These fields come together in the relatively new area of psychoneuroimmunolgy. This article examines some findings from these fields that are not widely discussed in the physical therapy professions. These findings are of relevance to many of the disciplines within the physical therapies. It is the authors aim to stimulate further interest in the relevant, yet often under explored areas of immunology and psychoneuroimmunology.
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Affiliation(s)
- Les Alford
- University of East Anglia, Queens Building, Norwich NR4 7TJ, UK.
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40
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Metwali A, Setiawan T, Blum AM, Urban J, Elliott DE, Hang L, Weinstock JV. Induction of CD8+ regulatory T cells in the intestine by Heligmosomoides polygyrus infection. Am J Physiol Gastrointest Liver Physiol 2006; 291:G253-9. [PMID: 16825660 DOI: 10.1152/ajpgi.00409.2005] [Citation(s) in RCA: 72] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
This study determined whether Heligmosomoides polygyrus induces intestinal regulatory T cells. Splenic T cells proliferate strongly when cultured with anti-CD3 and antigen-presenting cells (APC). Lamina propria T cells from mice with H. polygyrus mixed with normal splenic T cells from uninfected mice inhibited proliferation over 90%. Lamina propria T cells from mice without H. polygyrus only modestly affected T cell proliferation. The worm-induced regulatory T cell was CD8+ and required splenic T cell contact to inhibit proliferation. The regulation also was IL-10 independent, but TAP-dependent, suggesting that it requires major histocompatibility complex (MHC) class I interaction. Additional studies employed mice with transgenic T cells that did not express functional TGF-beta receptors. The lamina propria T regulator inhibited proliferation of these transgenic T cells nearly 100%, suggesting that TGF-beta signaling via the T cell was not required. CD8+ T cells were needed for worms to reverse piroxicam-induced colitis in Rag mice (T and B cell deficient) reconstituted with IL-10-/- T cells. Thus H. polygyrus induces a regulatory CD8+ lamina propria T cell that inhibits T cell proliferation and that appears to have a role in control of colitis.
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Affiliation(s)
- Ahmed Metwali
- Department of Internal Medicine, University of Iowa, Iowa City, USA
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41
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Abstract
The helminth glycan LNFPIII is an immunomodulatory molecule, driving CD4(+) Th2-type biasing as well as immune suppression. Psoriasis is an autoimmune disease where the immune mechanisms as well as the antigens responsible for development of immune autoreactivity are still not known. In the absence of defined immunological mechanisms, we asked whether LNFPIII would function as novel therapy for psoriasis. We tested the therapeutic efficacy of LNFPIII using the flaky skin (fsn)/fsn mutant mouse model of psoriasis-like lesion development. We found that treatment of mice with LNFPIII prevented the appearance of psoriatic skin lesions on fsn/fsn mice. Examination of the skin 2 weeks after treatment demonstrated that prevention of skin lesions was associated with maintenance of normal epidermis thickness in LNFPIII-treated mice as compared with a significantly thickened epidermis in control treated and diseased mice. In addition, cells from skin of LNFPIII-treated mice produced lower amounts of interferon-gamma as compared with cells from skin of control treated diseased mice. Examination of macrophages and T cells from peripheral lymph nodes of control and LNFPIII-treated fsn/fsn mice showed that glycan treatment reduced the numbers of Gr1(+)F4/80(+) macrophages and the numbers of CD8(+) T cells, restoring the numbers of these two cell populations as well as the CD4 : CD8 ratio to near normal levels. Overall, the results from this study suggest that the helminth immunomodulatory glycan LNFPIII functions to prevent development of psoriatic-like skin lesions in fsn/fsn mice.
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Affiliation(s)
- Olga Atochina
- Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
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42
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Bloomfield SF, Stanwell-Smith R, Crevel RWR, Pickup J. Too clean, or not too clean: the hygiene hypothesis and home hygiene. Clin Exp Allergy 2006; 36:402-25. [PMID: 16630145 PMCID: PMC1448690 DOI: 10.1111/j.1365-2222.2006.02463.x] [Citation(s) in RCA: 136] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The 'hygiene hypothesis' as originally formulated by Strachan, proposes that a cause of the recent rapid rise in atopic disorders could be a lower incidence of infection in early childhood, transmitted by unhygienic contact with older siblings. Use of the term 'hygiene hypothesis' has led to several interpretations, some of which are not supported by a broader survey of the evidence. The increase in allergic disorders does not correlate with the decrease in infection with pathogenic organisms, nor can it be explained by changes in domestic hygiene. A consensus is beginning to develop round the view that more fundamental changes in lifestyle have led to decreased exposure to certain microbial or other species, such as helminths, that are important for the development of immunoregulatory mechanisms. Although this review concludes that the relationship of the hypothesis to hygiene practice is not proven, it lends strong support to initiatives seeking to improve hygiene practice. It would however be helpful if the hypothesis were renamed, e.g. as the 'microbial exposure' hypothesis, or 'microbial deprivation' hypothesis, as proposed for instance by Bjorksten. Avoiding the term 'hygiene' would help focus attention on determining the true impact of microbes on atopic diseases, while minimizing risks of discouraging good hygiene practice.
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Affiliation(s)
- S F Bloomfield
- London School of Hygiene and Tropical Medicine, London, UK.
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43
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Abstract
Gastrointestinal (GI) nematodes are incredibly successful parasites. Choosing to live in an exposed extracellular niche, in confrontation with a potentially hostile environment, their persistent, chronic lifestyle is persuasive evidence in itself for their profound ability to modulate their hosts' immune response. Modulation is essential to avoid their own destruction but also subtly balanced to avoid compromising host survival. This review describes the early circumstantial evidence that gave clues to the immunomodulatory capabilities of the GI nematodes, the roles that T regulatory cells and alternatively activated macrophages play in this immunomodulation and provides examples of the types of specific parasite-derived factors that are known to modulate host immunity, potentiating parasite survival.
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Affiliation(s)
- K J Else
- Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
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44
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Summers RW, Elliott DE, Weinstock JV. Is there a role for helminths in the therapy of inflammatory bowel disease? ACTA ACUST UNITED AC 2005; 2:62-3. [PMID: 16265104 DOI: 10.1038/ncpgasthep0087] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2004] [Accepted: 12/14/2004] [Indexed: 01/15/2023]
Affiliation(s)
- Robert W Summers
- James A Clifton Center for Digestive Disease, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City 52242, USA.
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45
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Hunt JRF, Martinelli R, Adams VC, Rook GAW, Brunet LR. Intragastric administration of Mycobacterium vaccae inhibits severe pulmonary allergic inflammation in a mouse model. Clin Exp Allergy 2005; 35:685-90. [PMID: 15898994 DOI: 10.1111/j.1365-2222.2005.02239.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Coexistence with harmless microorganisms such as lactobacilli, saprophytic mycobacteria and some helminths, throughout evolution, may have shaped the host immune system. Exposure to such organisms may have therapeutic benefits by triggering immunoregulatory mechanisms that control inappropriate immune responses to self, gut contents or allergens. OBJECTIVE We determined whether treatment with Mycobacterium vaccae by gavage influences the host immune response both locally and systemically. We also investigated whether delivery by this route prevents severe symptoms of disease in a murine model of pulmonary allergic inflammation. RESULTS A single intragastric administration of M. vaccae induced a transient increase in the production of IL-10 and IFN-gamma by mesenteric lymph nodes cells and splenocytes. In addition, in a mouse model of pulmonary allergic inflammation, a single treatment with M. vaccae by gavage not only diminished the total cellular infiltrate and the eosinophilic component induced by subsequent intratracheal allergen challenge, but also biased local and systemic cytokine production towards IL-10. Delivery of M. vaccae by gavage was as effective as subcutaneous treatment. CONCLUSION This is the first report to suggest that heat-killed mycobacteria can down-regulate symptoms of allergic inflammation by the intragastric route. These data suggest an alternative route of treatment with M. vaccae for patients with allergic conditions.
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46
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Mulcahy G, O'Neill S, Fanning J, McCarthy E, Sekiya M. Tissue migration by parasitic helminths – an immunoevasive strategy? Trends Parasitol 2005; 21:273-7. [PMID: 15922248 DOI: 10.1016/j.pt.2005.04.003] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Revised: 02/04/2005] [Accepted: 04/11/2005] [Indexed: 11/25/2022]
Abstract
Migration through host tissues has major costs for parasitic helminths in terms of energy expenditure, risks of attrition and the need to adapt to varying physicochemical environments. Nevertheless, such migratory phases seem to confer a specific survival advantage. One reason for this might be the avoidance of specific host immune-defence mechanisms designed to protect against threats at mucosal surfaces.
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Affiliation(s)
- Grace Mulcahy
- Department of Veterinary Microbiology and Parasitology, Faculty of Veterinary Medicine and Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
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47
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Abstract
Asthma has reached epidemic proportions globally. This has been attributed by many to improved hygiene. The frequent failure of conventional pharmaceuticals to manage the disease has led to the introduction of parasites as a potential alternative therapy for asthma and other immunological diseases. In this article, we briefly review the immunological rationale underpinning therapeutic parasitic infection, describe recently initiated trials, and highlight potential risks and benefits of introducing parasites into patient cohorts.
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Affiliation(s)
- Franco H Falcone
- Immune Modulation Research Group, School of Pharmacy, University Park, Nottingham NG7 2RD, UK
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48
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Kirsner JB. Inflammatory bowel diseases at the University of Chicago--early experiences: a personal historical account. Inflamm Bowel Dis 2005; 11:407-16. [PMID: 15803033 DOI: 10.1097/01.mib.0000164101.96028.ac] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Joseph B Kirsner
- Department of Medicine, The University of Chicago, Chicago, Illinois 60637-4700, USA.
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49
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Fessler DMT, Abrams ET. Infant mouthing behavior: the immunocalibration hypothesis. Med Hypotheses 2005; 63:925-32. [PMID: 15504558 DOI: 10.1016/j.mehy.2004.08.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2004] [Accepted: 08/05/2004] [Indexed: 11/15/2022]
Abstract
Avid mouthing, the propensity of infants to suck objects and put them in their mouths, is a pattern characteristic of the first 2-3 years of life, with its most intensive manifestation occurring during the first year. Although traditional accounts explain infant mouthing as a source of sensual gratification and/or environmental exploration, these proximate hypotheses are inconsistent with the high costs of mouthing, including choking, poisoning, and exposure to pathogens. We propose that mouthing serves to proactively expose the naive gastrointestinal tract to environmental antigens and commensal bacteria while under the sheltering umbrella of breastfeeding. Mouthing functions to accurately calibrate the developing immune system, including antibody production and mucosal immunity, to the local disease ecology. The critical exposure period is not open-ended, as failure to expose the gut to an adequate number of antigens early in life is associated with an increased risk of allergies, asthma, and atopy. Weaning initiates a number of immune changes that may program the neonatal immune system into certain life-long responses.
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Affiliation(s)
- Daniel M T Fessler
- Department of Anthropology, 341 Haines Hall, University of California, Los Angeles, CA 90095-1553, USA.
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50
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Abstract
Two distinct, but rapidly converging, areas of research (the hygiene hypothesis and the study of probiotic/prebiotic effects) have emphasised the need to understand, and ultimately to manipulate, our physiological interactions with commensal flora, and with other transient but harmless organisms from the environment that affect immunoregulatory circuits. The story began with allergic disorders but now inflammatory bowel disease is increasingly involved.
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Affiliation(s)
- G A W Rook
- Centre for Infectious Diseases and International Health, Windeyer Institute of Medical Sciences, Royal Free and University College Medical School, 46 Cleveland St, London W1T 4JF, UK.
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