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Djebbara S, Belguendouz H, Soufli I, Hannachi L, Ameur F, Benazzouz S, Benkhelifa S, Terrahi M, Achour K, Amir ZC, Amri M, Touil-Boukoffa C. Laminated Layer Extract from Echinococcus Granulosus cyst Attenuates Ocular Damages and Inflammatory Responses in an Experimental Autoimmune Uveitis Model. Acta Parasitol 2025; 70:34. [PMID: 39853513 DOI: 10.1007/s11686-024-00944-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 12/19/2024] [Indexed: 01/26/2025]
Abstract
PURPOSE Since extract of the laminated layer (LL) from E. granulosus showed immuno-modulatory effects in vitro and in vivo, we sought to determine its effect on the onset, development, and evolution of experimental auto-immune uveitis (EAU). The latter is a model of some human diseases with ocular inflammation that can cause blindness. METHODS E. granulosus LL extract was either injected before EAU induction for the pretreated group or later for treated group. Ocular exploration was made by retinal histological and immunohistological (CD86, CD4, CD8) analysis. Myeloperoxidase (MPO), Superoxide dismutase (SOD), Catalase enzymatic activities (CAT), and Malondialdehyde (MDA), Nitric oxide (NO), Urea, and TNF-α levels were measured in plasma. RESULTS LL injection attenuated retinal histological damage and reduced cells infiltration. Also, LL decreased systemic inflammatory and oxidative markers as well as TNF-α production and increased antioxidant parameters. CONCLUSIONS Interestingly, we observed a protective effect of E. granulosus LL extract during EAU. LL appears to ameliorate retinal damage by down-regulating inflammatory responses. Our results support LL immunomodulatory effects during autoimmune diseases and offer a promising prospect for helminthic therapy during autoimmune uveitis.
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Affiliation(s)
- Sara Djebbara
- Cytokines and NO Synthases Team, LBCM, FSB, USTHB, BP 32 El Alia, Bab Ezzouar, Algiers, 16111, Algeria
| | - Houda Belguendouz
- Cytokines and NO Synthases Team, LBCM, FSB, USTHB, BP 32 El Alia, Bab Ezzouar, Algiers, 16111, Algeria
| | - Imene Soufli
- Cytokines and NO Synthases Team, LBCM, FSB, USTHB, BP 32 El Alia, Bab Ezzouar, Algiers, 16111, Algeria
| | - Leila Hannachi
- Department of Pathological Anatomy, University Hospital Center Mustapha Pacha, Algiers, Algeria
| | - Fahima Ameur
- Cytokines and NO Synthases Team, LBCM, FSB, USTHB, BP 32 El Alia, Bab Ezzouar, Algiers, 16111, Algeria
| | - Sara Benazzouz
- Institute of Parasitology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, CH-3012, Bern, Switzerland
| | - Sarra Benkhelifa
- Cytokines and NO Synthases Team, LBCM, FSB, USTHB, BP 32 El Alia, Bab Ezzouar, Algiers, 16111, Algeria
| | - Malika Terrahi
- Department of Ophthalmology, University Hospital Center Nafissa Hammoud, Algiers, Algeria
| | - Karima Achour
- Thoracic Surgery Department, University Hospital Center Bab El Oued, Algiers, Algeria
| | - Zine-Charaf Amir
- Department of Pathological Anatomy, University Hospital Center Mustapha Pacha, Algiers, Algeria
| | - Manel Amri
- Cytokines and NO Synthases Team, LBCM, FSB, USTHB, BP 32 El Alia, Bab Ezzouar, Algiers, 16111, Algeria
| | - Chafia Touil-Boukoffa
- Cytokines and NO Synthases Team, LBCM, FSB, USTHB, BP 32 El Alia, Bab Ezzouar, Algiers, 16111, Algeria.
- Algerian Academy for Science and Technology (AAST), Algiers, Algeria.
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Pandey H, Tang DWT, Wong SH, Lal D. Helminths in alternative therapeutics of inflammatory bowel disease. Intest Res 2025; 23:8-22. [PMID: 39916482 PMCID: PMC11834367 DOI: 10.5217/ir.2023.00059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 10/24/2023] [Accepted: 11/01/2023] [Indexed: 02/20/2025] Open
Abstract
Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a nonspecific chronic inflammation of the gastrointestinal tract. Despite recent advances in therapeutics and newer management strategies, IBD largely remains untreatable. Helminth therapy is a promising alternative therapeutic for IBD that has gained some attention in the last two decades. Helminths have immunomodulatory effects and can alter the gut microbiota. The immunomodulatory effects include a strong Th2 immune response, T-regulatory cell response, and the production of regulatory cytokines. Although concrete evidence regarding the efficacy of helminth therapy in IBD is lacking, clinical studies and studies done in animal models have shown some promise. Most clinical studies have shown that helminth therapy is safe and easily tolerable. Extensive work has been done on the whipworm Trichuris, but other helminths, including Schistosoma, Trichinella, Heligmosomoides, and Ancylostoma, have also been explored for pre-clinical and animal studies. This review article summarizes the potential of helminth therapy as an alternative therapeutic or an adjuvant to the existing therapeutic procedures for IBD treatment.
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Affiliation(s)
| | - Daryl W. T. Tang
- School of Biological Sciences, Nanyang Technological University, Singapore
| | - Sunny H. Wong
- Centre for Microbiome Medicine, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Devi Lal
- Department of Zoology, Ramjas College, University of Delhi, Delhi, India
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Tjandra D, Busuttil RA, Boussioutas A. Gastric Intestinal Metaplasia: Challenges and the Opportunity for Precision Prevention. Cancers (Basel) 2023; 15:3913. [PMID: 37568729 PMCID: PMC10417197 DOI: 10.3390/cancers15153913] [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: 06/28/2023] [Revised: 07/20/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
GIM is a persistent, premalignant lesion whereby gastric mucosa is replaced by metaplastic mucosa resembling intestinal tissue, arising in the setting of chronic inflammation, particularly in the context of Helicobacter pylori. While the overall rates of progression to gastric adenocarcinoma are low, estimated at from 0.25 to 2.5%, there are features that confer a much higher risk and warrant follow-up. In this review, we collate and summarise the current knowledge regarding the pathogenesis of GIM, and the clinical, endoscopic and histologic risk factors for cancer. We examine the current state-of-practice with regard to the diagnosis and management of GIM, which varies widely in the published guidelines and in practice. We consider the emerging evidence in population studies, artificial intelligence and molecular markers, which will guide future models of care. The ultimate goal is to increase the detection of early gastric dysplasia/neoplasia that can be cured while avoiding unnecessary surveillance in very low-risk individuals.
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Affiliation(s)
- Douglas Tjandra
- Central Clinical School, Monash University, 99 Commercial Rd, Melbourne, VIC 3004, Australia;
- Department of Gastroenterology, The Alfred Hospital, 55 Commercial Rd, Melbourne, VIC 3004, Australia
| | - Rita A. Busuttil
- Central Clinical School, Monash University, 99 Commercial Rd, Melbourne, VIC 3004, Australia;
- Department of Gastroenterology, The Alfred Hospital, 55 Commercial Rd, Melbourne, VIC 3004, Australia
| | - Alex Boussioutas
- Central Clinical School, Monash University, 99 Commercial Rd, Melbourne, VIC 3004, Australia;
- Department of Gastroenterology, The Alfred Hospital, 55 Commercial Rd, Melbourne, VIC 3004, Australia
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Zhang Y, Hardy LC, Kapita CM, Hall JA, Arbeeva L, Campbell E, Urban JF, Belkaid Y, Nagler CR, Iweala OI. Intestinal Helminth Infection Impairs Oral and Parenteral Vaccine Efficacy. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2023; 211:389-402. [PMID: 37272847 PMCID: PMC10524302 DOI: 10.4049/jimmunol.2300084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 05/18/2023] [Indexed: 06/06/2023]
Abstract
The impact of endemic parasitic infection on vaccine efficacy is an important consideration for vaccine development and deployment. We have examined whether intestinal infection with the natural murine helminth Heligmosomoides polygyrus bakeri alters Ag-specific Ab and cellular immune responses to oral and parenteral vaccination in mice. Oral vaccination of mice with a clinically relevant, live, attenuated, recombinant Salmonella vaccine expressing chicken egg OVA (Salmonella-OVA) induced the accumulation of activated, OVA-specific T effector cells rather than OVA-specific regulatory T cells in the GALT. Intestinal helminth infection significantly reduced Th1-skewed Ab responses to oral vaccination with Salmonella-OVA. Activated, adoptively transferred, OVA-specific CD4+ T cells accumulated in draining mesenteric lymph nodes of vaccinated mice, regardless of their helminth infection status. However, helminth infection increased the frequencies of adoptively transferred OVA-specific CD4+ T cells producing IL-4 and IL-10 in the mesenteric lymph node. Ab responses to the oral Salmonella-OVA vaccine were reduced in helminth-free mice adoptively transferred with OVA-specific CD4+ T cells harvested from mice with intestinal helminth infection. Intestinal helminth infection also significantly reduced Th2-skewed Ab responses to parenteral vaccination with OVA adsorbed to alum. These findings suggest that vaccine-specific CD4+ T cells induced in the context of helminth infection retain durable immunomodulatory properties and may promote blunted Ab responses to vaccination. They also underscore the potential need to treat parasitic infection before mass vaccination campaigns in helminth-endemic areas.
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Affiliation(s)
- Yugen Zhang
- Department of Medicine, Thurston Arthritis Research Center, Division of Rheumatology, Allergy, and Immunology, Chapel Hill, NC, 27599
- Department of Pediatrics, University of North Carolina Food Allergy Initiative, Division of Allergy and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, 27599
| | - LaKeya C. Hardy
- Department of Medicine, Thurston Arthritis Research Center, Division of Rheumatology, Allergy, and Immunology, Chapel Hill, NC, 27599
- Department of Pediatrics, University of North Carolina Food Allergy Initiative, Division of Allergy and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, 27599
| | - Camille M. Kapita
- Department of Medicine, Thurston Arthritis Research Center, Division of Rheumatology, Allergy, and Immunology, Chapel Hill, NC, 27599
| | - Jason A. Hall
- National Institute of Allergy and Infectious Diseases Microbiome Program and Metaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, Center for Human Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
| | - Liubov Arbeeva
- Department of Medicine, Thurston Arthritis Research Center, Division of Rheumatology, Allergy, and Immunology, Chapel Hill, NC, 27599
| | - Evelyn Campbell
- Biological Sciences Division, University of Chicago, Chicago, IL, 60637
| | - Joseph F. Urban
- United States Department of Agriculture, Agricultural Research Service, Beltsville Agricultural Research Center, Animal Parasitic Diseases Laboratory and Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, 10300 Baltimore Avenue BLDG 307-C BARC-East, Beltsville, MD, 20705
| | - Yasmine Belkaid
- National Institute of Allergy and Infectious Diseases Microbiome Program and Metaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, Center for Human Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
| | - Cathryn R. Nagler
- Biological Sciences Division, University of Chicago, Chicago, IL, 60637
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637
- Center for Immunology and Inflammatory Disease, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Charlestown, MA 02129
| | - Onyinye I. Iweala
- Department of Medicine, Thurston Arthritis Research Center, Division of Rheumatology, Allergy, and Immunology, Chapel Hill, NC, 27599
- Department of Pediatrics, University of North Carolina Food Allergy Initiative, Division of Allergy and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, 27599
- Center for Immunology and Inflammatory Disease, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Charlestown, MA 02129
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Zhao B, Osbelt L, Lesker TR, Wende M, Galvez EJC, Hönicke L, Bublitz A, Greweling-Pils MC, Grassl GA, Neumann-Schaal M, Strowig T. Helicobacter spp. are prevalent in wild mice and protect from lethal Citrobacter rodentium infection in the absence of adaptive immunity. Cell Rep 2023; 42:112549. [PMID: 37245209 DOI: 10.1016/j.celrep.2023.112549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 03/15/2023] [Accepted: 05/04/2023] [Indexed: 05/30/2023] Open
Abstract
Transfer of the gut microbiota from wild to laboratory mice alters the host's immune status and enhances resistance to infectious and metabolic diseases, but understanding of which microbes and how they promote host fitness is only emerging. Our analysis of metagenomic sequencing data reveals that Helicobacter spp. are enriched in wild compared with specific-pathogen-free (SPF) and conventionally housed mice, with multiple species commonly co-colonizing their hosts. We create laboratory mice harboring three non-SPF Helicobacter spp. to evaluate their effect on mucosal immunity and colonization resistance to the enteropathogen Citrobacter rodentium. Our experiments reveal that Helicobacter spp. interfere with C. rodentium colonization and attenuate C. rodentium-induced gut inflammation in wild-type (WT) mice, even preventing lethal infection in Rag2-/- SPF mice. Further analyses suggest that Helicobacter spp. interfere with tissue attachment of C. rodentium, putatively by reducing the availability of mucus-derived sugars. These results unveil pivotal protective functions of wild mouse microbiota constituents against intestinal infection.
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Affiliation(s)
- Bei Zhao
- Department of Microbial Immune Regulation, Helmholtz Center for Infection Research, Braunschweig, Germany
| | - Lisa Osbelt
- Department of Microbial Immune Regulation, Helmholtz Center for Infection Research, Braunschweig, Germany; ESF International Graduate School on Analysis, Imaging, and Modelling of Neuronal and Inflammatory Processes, Otto von Guericke University, Magdeburg, Germany
| | - Till Robin Lesker
- Department of Microbial Immune Regulation, Helmholtz Center for Infection Research, Braunschweig, Germany
| | - Marie Wende
- Department of Microbial Immune Regulation, Helmholtz Center for Infection Research, Braunschweig, Germany; ESF International Graduate School on Analysis, Imaging, and Modelling of Neuronal and Inflammatory Processes, Otto von Guericke University, Magdeburg, Germany
| | - Eric J C Galvez
- Department of Microbial Immune Regulation, Helmholtz Center for Infection Research, Braunschweig, Germany
| | - Lisa Hönicke
- Department of Microbial Immune Regulation, Helmholtz Center for Infection Research, Braunschweig, Germany
| | - Arne Bublitz
- Department of Microbial Immune Regulation, Helmholtz Center for Infection Research, Braunschweig, Germany
| | | | - Guntram A Grassl
- Department of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany; German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany
| | - Meina Neumann-Schaal
- Bacterial Metabolomics, Leibniz Institute DSMZ - German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany
| | - Till Strowig
- Department of Microbial Immune Regulation, Helmholtz Center for Infection Research, Braunschweig, Germany; German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany; Centre for Individualized Infection Medicine (CiiM), A Joint Venture Between the Helmholtz Center for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.
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6
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Reyes VE. Helicobacter pylori and Its Role in Gastric Cancer. Microorganisms 2023; 11:1312. [PMID: 37317287 PMCID: PMC10220541 DOI: 10.3390/microorganisms11051312] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 05/08/2023] [Accepted: 05/15/2023] [Indexed: 06/16/2023] Open
Abstract
Gastric cancer is a challenging public health concern worldwide and remains a leading cause of cancer-related mortality. The primary risk factor implicated in gastric cancer development is infection with Helicobacter pylori. H. pylori induces chronic inflammation affecting the gastric epithelium, which can lead to DNA damage and the promotion of precancerous lesions. Disease manifestations associated with H. pylori are attributed to virulence factors with multiple activities, and its capacity to subvert host immunity. One of the most significant H. pylori virulence determinants is the cagPAI gene cluster, which encodes a type IV secretion system and the CagA toxin. This secretion system allows H. pylori to inject the CagA oncoprotein into host cells, causing multiple cellular perturbations. Despite the high prevalence of H. pylori infection, only a small percentage of affected individuals develop significant clinical outcomes, while most remain asymptomatic. Therefore, understanding how H. pylori triggers carcinogenesis and its immune evasion mechanisms is critical in preventing gastric cancer and mitigating the burden of this life-threatening disease. This review aims to provide an overview of our current understanding of H. pylori infection, its association with gastric cancer and other gastric diseases, and how it subverts the host immune system to establish persistent infection.
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Affiliation(s)
- Victor E Reyes
- Department of Pediatrics and Microbiology & Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0372, USA
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7
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Setshedi M, Watermeyer G. The impact of Helicobacter pylori and intestinal helminth infections on gastric adenocarcinoma and inflammatory bowel disease in Sub-Saharan Africa. Front Med (Lausanne) 2022; 9:1013779. [PMID: 36569142 PMCID: PMC9780450 DOI: 10.3389/fmed.2022.1013779] [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: 08/07/2022] [Accepted: 11/28/2022] [Indexed: 12/13/2022] Open
Abstract
Gastric adenocarcinoma (GCA) is the 5th leading cancer globally with an estimated 1.1 million cases reported in 2020. Ninety percent of non-cardia GCAs are attributable to Helicobacter pylori (H. pylori), the most prevalent bacterial infection globally. Rates of H. pylori infection are highest in Sub-Saharan Africa (SSA), yet surprisingly low numbers of GCAs are reported in the region. A similar phenomenon is seen with the inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis. These disorders have risen dramatically over the past century in high income countries across the globe, with sharp increases noted more recently in newly industrialized regions. In contrast IBD is rare in most regions in SSA. For both diseases this may reflect under-reporting or limited access to diagnostic modalities, but an alternative explanation is the high burden of infection with gastrointestinal parasites endemic to SSA which may attenuate the risk of developing GCA and IBD. In this mini review we discuss the complex interplay between these microorganisms, GCA, and IBD, as well as a possible protective role of H. pylori and the development of IBD.
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Jiao JY, Zhu XJ, Zhou C, Wang P. Research progress on the immune microenvironment of the gallbladder in patients with cholesterol gallstones. World J Gastrointest Surg 2022; 14:887-895. [PMID: 36185563 PMCID: PMC9521471 DOI: 10.4240/wjgs.v14.i9.887] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 08/19/2022] [Accepted: 09/07/2022] [Indexed: 02/07/2023] Open
Abstract
Cholesterol gallstones are very common in hepatobiliary surgery and have been studied to a certain extent by doctors worldwide for decades. However, the mechanism of cholesterol gallstone formation is not fully understood, so there is currently no completely effective drug for the treatment and prevention of cholesterol gallstones. The formation and development of cholesterol gallstones are caused by a variety of genetic and environmental factors, among which genetic susceptibility, intestinal microflora disorders, impaired gallbladder motility, and immune disorders are important in the pathogenesis of cholesterol gallstones. This review focuses on recent advances in these mechanisms. We also discuss some new targets that may be effective in the treatment and prevention of cholesterol gallstones, which may be hot areas in the future.
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Affiliation(s)
- Jing-Yi Jiao
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
- Medical School, Nantong University, Nantong 226001, Jiangsu Province, China
| | - Xiao-Jun Zhu
- Department of Hepatobiliary Surgery, Nantong First People's Hospital, Nantong 226001, Jiangsu Province, China
| | - Chun Zhou
- Department of General Practitioner, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Peng Wang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
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Yeshi K, Ruscher R, Loukas A, Wangchuk P. Immunomodulatory and biological properties of helminth-derived small molecules: Potential applications in diagnostics and therapeutics. FRONTIERS IN PARASITOLOGY 2022; 1:984152. [PMID: 39816468 PMCID: PMC11731824 DOI: 10.3389/fpara.2022.984152] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 08/23/2022] [Indexed: 01/18/2025]
Abstract
Parasitic helminths secrete and excrete a vast array of molecules known to help skew or suppress the host's immune response, thereby establishing a niche for sustained parasite maintenance. Indeed, the immunomodulatory potency of helminths is attributed mainly to excretory/secretory products (ESPs). The ESPs of helminths and the identified small molecules (SM) are reported to have diverse biological and pharmacological properties. The available literature reports only limited metabolites, and the identity of many metabolites remains unknown due to limitations in the identification protocols and helminth-specific compound libraries. Many metabolites are known to be involved in host-parasite interactions and pathogenicity. For example, fatty acids (e.g., stearic acid) detected in the infective stages of helminths are known to have a role in host interaction through facilitating successful penetration and migration inside the host. Moreover, excreted/secreted SM detected in helminth species are found to possess various biological properties, including anti-inflammatory activities, suggesting their potential in developing immunomodulatory drugs. For example, helminths-derived somatic tissue extracts and whole crude ESPs showed anti-inflammatory properties by inhibiting the secretion of proinflammatory cytokines from human peripheral blood mononuclear cells and suppressing the pathology in chemically-induced experimental mice model of colitis. Unlike bigger molecules like proteins, SM are ideal candidates for drug development since they are small structures, malleable, and lack immunogenicity. Future studies should strive toward identifying unknown SM and isolating the under-explored niche of helminth metabolites using the latest metabolomics technologies and associated software, which hold potential keys for finding new diagnostics and novel therapeutics.
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Affiliation(s)
- Karma Yeshi
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine (AITHM), James Cook University, Cairns, QLD, Australia
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Taghipour A, Bahadory S, Badri M, Yadegar A, Mirsamadi ES, Mirjalali H, Zali MR. A systematic review and meta-analysis on the co-infection of Helicobacter pylori with intestinal parasites: public health issue or neglected correlation? INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2022; 32:808-818. [PMID: 32729738 DOI: 10.1080/09603123.2020.1798890] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Accepted: 07/16/2020] [Indexed: 06/11/2023]
Abstract
The current study was conducted to assess the prevalence and odds ratio (OR) of co-infection of Helicobacter pylori (H. pylori) and intestinal parasites (IPs). English databases were searched. A total of 18 studies including 14 studies with cross-sectional design (a total of 3739 participants) and 4 studies with case-control design (397 patients and 320 controls) met the eligibility criteria. The pooled prevalence of H. pylori, intestinal parasite infections (IPIs), and their co-infections in different populations were 48.3% (95% CI, 34.1-62.8%), 15.4% (95% CI, 10-22.8%), and 11% (95% CI, 6.7-17.6%), respectively. The co-infection of H. pylori and Giardia was 7.6% (95% CI, 4.9-11.7%). Although statistically not significant, the risk of co-infection of H. pylori and IPIs was higher in case group compared to control group (OR, 1.59; 95% CI, 0.77-3.25). The overlaps between H. pylori and IPIs in countries with lower human development index (HDI) and income levels were high.
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Affiliation(s)
- Ali Taghipour
- Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Saeed Bahadory
- Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Milad Badri
- Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Elnaz Sadat Mirsamadi
- Department of Microbiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Hamed Mirjalali
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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11
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Mitigation of Toxoplasma gondii-induced ileitis by Trichinellaspiralis infection pinpointing immunomodulation. J Parasit Dis 2022; 46:491-501. [DOI: 10.1007/s12639-022-01476-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 02/09/2022] [Indexed: 10/18/2022] Open
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12
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Aziz F, Khan I, Shukla S, Dey DK, Yan Q, Chakraborty A, Yoshitomi H, Hwang SK, Sonwal S, Lee H, Haldorai Y, Xiao J, Huh YS, Bajpai VK, Han YK. Partners in crime: The Lewis Y antigen and fucosyltransferase IV in Helicobacter pylori-induced gastric cancer. Pharmacol Ther 2021; 232:107994. [PMID: 34571111 DOI: 10.1016/j.pharmthera.2021.107994] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 09/09/2021] [Accepted: 09/13/2021] [Indexed: 02/05/2023]
Abstract
Helicobacter pylori (H. pylori) is a major causative agent of chronic gastritis, gastric ulcer and gastric carcinoma. H. pylori cytotoxin associated antigen A (CagA) plays a crucial role in the development of gastric cancer. Gastric cancer is associated with glycosylation alterations in glycoproteins and glycolipids on the cell surface. H. pylori cytotoxin associated antigen A (CagA) plays a significant role in the progression of gastric cancer through post-translation modification of fucosylation to develop gastric cancer. The involvement of a variety of sugar antigens in the progression and development of gastric cancer has been investigated, including type II blood group antigens. Lewis Y (LeY) is overexpressed on the tumor cell surface either as a glycoprotein or glycolipid. LeY is a difucosylated oligosaccharide, which is catalyzed by fucosyltransferases such as FUT4 (α1,3). FUT4/LeY overexpression may serve as potential correlative biomarkers for the prognosis of gastric cancer. We discuss the various aspects of H. pylori in relation to fucosyltransferases (FUT1-FUT9) and its fucosylated Lewis antigens (LeY, LeX, LeA, and LeB) and gastric cancer. In this review, we summarize the carcinogenic effect of H. pylori CagA in association with LeY and its synthesis enzyme FUT4 in the development of gastric cancer as well as discuss its importance in the prognosis and its inhibition by combination therapy of anti-LeY antibody and celecoxib through MAPK signaling pathway preventing gastric carcinogenesis.
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Affiliation(s)
- Faisal Aziz
- The Hormel Institute-University of Minnesota, Austin, MN 55912, USA; Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian 116044, PR China.
| | - Imran Khan
- The Hormel Institute-University of Minnesota, Austin, MN 55912, USA
| | - Shruti Shukla
- TERI-Deakin Nanobiotechnology Centre, The Energy and Resources Institute, Gwal Pahari, Gurugram, Haryana 122003, India
| | - Debasish Kumar Dey
- Department of Biotechnology, College of Engineering, Daegu University, Gyeongsan 38453, Republic of Korea
| | - Qiu Yan
- Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian 116044, PR China
| | | | - Hisae Yoshitomi
- The Hormel Institute-University of Minnesota, Austin, MN 55912, USA
| | - Seung-Kyu Hwang
- Department of Biological Engineering, NanoBio High-Tech Materials Research Center, Inha University, 100 Inha-ro, Nam-gu, Incheon 22212, Republic of Korea
| | - Sonam Sonwal
- Department of Biological Engineering, NanoBio High-Tech Materials Research Center, Inha University, 100 Inha-ro, Nam-gu, Incheon 22212, Republic of Korea
| | - Hoomin Lee
- Department of Biological Engineering, NanoBio High-Tech Materials Research Center, Inha University, 100 Inha-ro, Nam-gu, Incheon 22212, Republic of Korea
| | - Yuvaraj Haldorai
- Department of Nanoscience and Technology, Bharathiar University, Coimbatore, Tamilnadu 641046, India
| | - Jianbo Xiao
- Institute of Food Safety and Nutrition, Jinan University, Guangzhou 510632, China; University of Vigo, Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Science, E32004 Ourense, Spain.
| | - Yun Suk Huh
- Department of Biological Engineering, NanoBio High-Tech Materials Research Center, Inha University, 100 Inha-ro, Nam-gu, Incheon 22212, Republic of Korea.
| | - Vivek K Bajpai
- Department of Energy and Materials Engineering, Dongguk University-Seoul, 30 Pildong-ro 1-gil, Seoul 04620, Republic of Korea.
| | - Young-Kyu Han
- Department of Energy and Materials Engineering, Dongguk University-Seoul, 30 Pildong-ro 1-gil, Seoul 04620, Republic of Korea.
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13
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Ahmed AFM, El-Sayad MH, Ali HS, El-Taweel HA. Impact of Coinfection with Schistosoma mansoni on the Antibody Response to Helicobacter pylori. Acta Parasitol 2021; 66:857-862. [PMID: 33598776 DOI: 10.1007/s11686-020-00330-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 12/15/2020] [Indexed: 11/26/2022]
Abstract
PURPOSE In many tropical areas, the coinfection of Schistosoma spp. and other pathogens is frequent. The impact of schistosomiasis on other infections has been demonstrated for several organisms. Infection with the widely spread bacterium, Helicobacter pylori, has been linked to ulcers and tumors of the digestive system with the humoral immune response playing possible modulatory roles. The present study investigated the impact of patent S. mansoni infection on the antibody response to H. pylori. METHODS A total of 100 participants from a schistosomiasis endemic area in Egypt were enrolled in the study. Based on the detection of S. mansoni eggs and H. pylori coproantigen in fecal samples, they were equally divided into four groups: schistosomiasis, concomitant S. mansoni and H. pylori infection, H. pylori infection alone, and healthy controls. Anti-H. pylori IgG and IgA were determined in serum samples using ELISA. RESULTS A significantly lower IgA seropositivity rate and significantly lower IgG levels were found in patients with concomitant schistosomiasis (Gp2) compared to those infected only with H. pylori (Gp1). CONCLUSIONS Concomitant S. mansoni infection with light to moderate intensity alters serological responses to H. pylori. In schistosomiasis endemic areas, the routine examination for H. pylori infection should, therefore, rely on coproantigen level rather than antibody levels. Further studies should investigate histopathological changes and other immunological parameters in coinfection.
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Affiliation(s)
- Ashraf Fawzy Mosa Ahmed
- Parasitology Department, Medical Research Institute, Alexandria University, 165, Horreya Avenue, Hadara, Alexandria, Egypt
| | - Mona Hassan El-Sayad
- Parasitology Department, Medical Research Institute, Alexandria University, 165, Horreya Avenue, Hadara, Alexandria, Egypt
| | - Hala Shehata Ali
- Parasitology Department, Medical Research Institute, Alexandria University, 165, Horreya Avenue, Hadara, Alexandria, Egypt
| | - Hend Aly El-Taweel
- Parasitology Department, Medical Research Institute, Alexandria University, 165, Horreya Avenue, Hadara, Alexandria, Egypt.
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14
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Helicobacter pylori-Induced Inflammation: Possible Factors Modulating the Risk of Gastric Cancer. Pathogens 2021; 10:pathogens10091099. [PMID: 34578132 PMCID: PMC8467880 DOI: 10.3390/pathogens10091099] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/21/2021] [Accepted: 08/25/2021] [Indexed: 02/07/2023] Open
Abstract
Chronic inflammation and long-term tissue injury are related to many malignancies, including gastric cancer (GC). Helicobacter pylori (H. pylori), classified as a class I carcinogen, induces chronic superficial gastritis followed by gastric carcinogenesis. Despite a high prevalence of H. pylori infection, only about 1–3% of people infected with this bacterium develop GC worldwide. Furthermore, the development of chronic gastritis in some, but not all, H. pylori-infected subjects remains unexplained. These conflicting findings indicate that clinical outcomes of aggressive inflammation (atrophic gastritis) to gastric carcinogenesis are influenced by several other factors (in addition to H. pylori infection), such as gut microbiota, co-existence of intestinal helminths, dietary habits, and host genetic factors. This review has five goals: (1) to assess our current understanding of the process of H. pylori-triggered inflammation and gastric precursor lesions; (2) to present a hypothesis on risk modulation by the gut microbiota and infestation with intestinal helminths; (3) to identify the dietary behavior of the people at risk of GC; (4) to check the inflammation-related genetic polymorphisms and role of exosomes together with other factors as initiators of precancerous lesions and gastric carcinoma; and (5) finally, to conclude and suggest a new direction for future research.
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15
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Varon C, Azzi-Martin L, Khalid S, Seeneevassen L, Ménard A, Spuul P. Helicobacters and cancer, not only gastric cancer? Semin Cancer Biol 2021; 86:1138-1154. [PMID: 34425210 DOI: 10.1016/j.semcancer.2021.08.007] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 08/11/2021] [Accepted: 08/16/2021] [Indexed: 12/11/2022]
Abstract
The Helicobacter genus actually comprises 46 validly published species divided into two main clades: gastric and enterohepatic Helicobacters. These bacteria colonize alternative sites of the digestive system in animals and humans, and contribute to inflammation and cancers. In humans, Helicobacter infection is mainly related to H. pylori, a gastric pathogen infecting more than half of the world's population, leading to chronic inflammation of the gastric mucosa that can evolve into two types of gastric cancers: gastric adenocarcinomas and gastric MALT lymphoma. In addition, H. pylori but also non-H. pylori Helicobacter infection has been associated with many extra-gastric malignancies. This review focuses on H. pylori and its role in gastric cancers and extra-gastric diseases, as well as malignancies induced by non-H. pylori Helicobacters. Their different virulence factors and their involvement in carcinogenesis is discussed. This review highlights the importance of both gastric and enterohepatic Helicobacters in gastrointestinal and liver cancers.
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Affiliation(s)
- Christine Varon
- Univ. Bordeaux, INSERM, UMR1053 Bordeaux Research in Translational Oncology, BaRITOn, Bordeaux, France
| | - Lamia Azzi-Martin
- Univ. Bordeaux, INSERM, UMR1053 Bordeaux Research in Translational Oncology, BaRITOn, Bordeaux, France; Univ. Bordeaux, UFR des Sciences Médicales, Bordeaux, France
| | - Sadia Khalid
- Tallinn University of Technology, Department of Chemistry and Biotechnology, Akadeemia RD 15, 12618, Tallinn, Estonia
| | - Lornella Seeneevassen
- Univ. Bordeaux, INSERM, UMR1053 Bordeaux Research in Translational Oncology, BaRITOn, Bordeaux, France
| | - Armelle Ménard
- Univ. Bordeaux, INSERM, UMR1053 Bordeaux Research in Translational Oncology, BaRITOn, Bordeaux, France
| | - Pirjo Spuul
- Tallinn University of Technology, Department of Chemistry and Biotechnology, Akadeemia RD 15, 12618, Tallinn, Estonia.
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16
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Chen HL, Xing X, Zhang B, Huang HB, Shi CW, Yang GL, Wang CF. Higher mucosal type II immunity is associated with increased gut microbiota diversity in BALB/c mice after Trichinella spiralis infection. Mol Immunol 2021; 138:87-98. [PMID: 34364076 DOI: 10.1016/j.molimm.2021.07.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 07/08/2021] [Accepted: 07/13/2021] [Indexed: 01/22/2023]
Abstract
Understanding the interaction between the gut microbiota and Trichinella spiralis is of interest for the early diagnosis and development of therapeutics for trichinellosis and to reveal the potential role of microbiota in the mechanism of immunomodulation of this tissue-dwelling helminth. In this study, we utilized 16S rRNA gene sequencing to monitor the dynamics of the microbes in BALB/c mice challenged with T. spiralis. Flow cytometry and ELISA were used to analyze cytokines at the same time. Histopathological analysis of the duodenum was also conducted. We found that microbial perturbations occurred during infection. The abundance of the Lachnospiraceae NK4A136 group, Ruminococcus 1 and Lactococcus decreased. However, the abundance of proinflammatory Parabacteroides increased over time after infection. T. spiralis infection also tended to inhibit IFN-γ production, and promote IL-4 and IL-10 levels. In total, T. spiralis disrupts gut homeostasis and impairs the development of the intestinal ecosystem. Defining the bacterial populations affected by T. spiralis infection might help identify microbial markers for diagnosis of the disease, and the populations could also be further exploited as a novel option to treat T. spiralis infection.
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Affiliation(s)
- Hong-Liang Chen
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, China; Key Laboratory of Animal Production and Product Quality Safety of Ministry of Education, Jilin Agricultural University, Changchun, China
| | - Xin Xing
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, China; Key Laboratory of Animal Production and Product Quality Safety of Ministry of Education, Jilin Agricultural University, Changchun, China
| | - Bo Zhang
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, China; Key Laboratory of Animal Production and Product Quality Safety of Ministry of Education, Jilin Agricultural University, Changchun, China
| | - Hai-Bin Huang
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, China; Key Laboratory of Animal Production and Product Quality Safety of Ministry of Education, Jilin Agricultural University, Changchun, China
| | - Chun-Wei Shi
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, China; Key Laboratory of Animal Production and Product Quality Safety of Ministry of Education, Jilin Agricultural University, Changchun, China
| | - Gui-Lian Yang
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, China; Key Laboratory of Animal Production and Product Quality Safety of Ministry of Education, Jilin Agricultural University, Changchun, China.
| | - Chun-Feng Wang
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, China; Key Laboratory of Animal Production and Product Quality Safety of Ministry of Education, Jilin Agricultural University, Changchun, China.
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17
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Effect of Helicobacter pylori and Helminth Coinfection on the Immune Response to Mycobacterium tuberculosis. Curr Microbiol 2021; 78:3351-3371. [PMID: 34251513 DOI: 10.1007/s00284-021-02604-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Accepted: 06/30/2021] [Indexed: 02/07/2023]
Abstract
Tuberculosis remains one of the main causes of morbidity and mortality worldwide despite decades of efforts to eradicate the disease. Although the immune response controls the infection in most infected individuals (90%), the ability of the bacterium to persist throughout the host's life leads to a risk of reactivation. Underlying conditions including human immunodeficiency virus (HIV) infection, organ transplantation, and immunosuppressive therapies are considered risk factors for progression to active disease. However, many individuals infected with Mycobacterium tuberculosis may develop clinical disease in the absence of underlying immunosuppression. It is also possible that unknown conditions may drive the progression to disease. The human microbiota can be an important modulator of the immune system; it can not only trigger inflammatory disorders, but also drive the response to other infectious diseases. In developing countries, chronic mucosal infections with Helicobacter pylori and helminths may be particularly important, as these infections frequently coexist throughout the host's life. However, little is known about the interactions of these pathogens with the immune system and their effects on M. tuberculosis clinical disease, if any. In this review, we discuss the potential effects of H. pylori and helminth co-infections on the immune response to M. tuberculosis. This may contribute to our understanding of host-pathogen interactions and in designing new strategies for the prevention and control of tuberculosis.
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18
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Anand A, Fang HY, Mohammad-Shahi D, Ingermann J, Baumeister T, Strangmann J, Schmid RM, Wang TC, Quante M. Elimination of NF-κB signaling in Vimentin+ stromal cells attenuates tumorigenesis in a mouse model of Barrett's Esophagus. Carcinogenesis 2021; 42:405-413. [PMID: 33068426 DOI: 10.1093/carcin/bgaa109] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 09/29/2020] [Accepted: 10/13/2020] [Indexed: 12/16/2022] Open
Abstract
Chronic inflammation induces Barrett's Esophagus (BE) which can advance to esophageal adenocarcinoma. Elevated levels of interleukin (IL)-1b, IL-6 and IL-8 together with activated nuclear factor-kappaB (NF-κB), have been identified as important mediators of tumorigenesis. The inflammatory milieu apart from cancer cells and infiltrating immune cells contains myofibroblasts (MFs) that express aSMA and Vimentin. As we observed that increased NF-κB activation and inflammation correlates with increased MF recruitment and an accelerated phenotype we here analyze the role of NF-κB in MF during esophageal carcinogenesis in our L2-IL-1B mouse model. To analyze the effect of NF-κB signaling in MFs, we crossed L2-IL-1B mice to tamoxifen inducible Vim-Cre (Vim-CreTm) mice and floxed RelA (p65fl/fl) mice to specifically eliminate NF-κB signaling in MF (IL-1b.Vim-CreTm.p65fl/fl). The interaction of epithelial cells and stromal cells was further analyzed in mouse BE organoids and patient-derived human organoids. Histological scoring of IL-1b.Vim-CreTm.p65fl/fl mice showed a significantly attenuated phenotype compared with L2-IL-1B mice, with mild inflammation, decreased metaplasia and no dysplasia. This correlated with decreased proliferation and increased differentiation in cardia tissue of IL-1b.Vim-CreTm.p65fl/fl compared with L2-IL-1B mice. Distinct changes of cytokines and chemokines within the local microenvironment in IL-1b.Vim-CreTm.p65fl/fl mice reflected the histopathological abrogated phenotype. Co-cultured NF-κB inhibitor treated MF with mouse BE organoids demonstrated NF-κB-dependent growth and migration. MFs are essential to form an inflammatory and procarcinogenic microenvironment and NF-κB signaling in stromal cells emerges as an important driver of esophageal carcinogenesis. Our data suggest anti-inflammatory approaches as preventive strategies during surveillance of BE patients.
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Affiliation(s)
- Akanksha Anand
- Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), München, Germany
| | - Hsin-Yu Fang
- Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), München, Germany
| | - Donja Mohammad-Shahi
- Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), München, Germany
| | - Jonas Ingermann
- Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), München, Germany
| | - Theresa Baumeister
- Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), München, Germany
| | - Julia Strangmann
- Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), München, Germany
| | - Roland M Schmid
- Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), München, Germany
| | - Timothy C Wang
- Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
| | - Michael Quante
- Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), München, Germany.,Universitätsklinikum Freiburg, Klinik für Innere Medizin II, Hugstetter Straße 55, Freiburg, Germany
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19
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Palrasu M, Zaika E, El-Rifai W, Que J, Zaika AI. Role of Bacterial and Viral Pathogens in Gastric Carcinogenesis. Cancers (Basel) 2021; 13:1878. [PMID: 33919876 PMCID: PMC8070847 DOI: 10.3390/cancers13081878] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/02/2021] [Accepted: 04/11/2021] [Indexed: 01/10/2023] Open
Abstract
Gastric cancer (GC) is one of the deadliest malignancies worldwide. In contrast to many other tumor types, gastric carcinogenesis is tightly linked to infectious events. Infections with Helicobacter pylori (H. pylori) bacterium and Epstein-Barr virus (EBV) are the two most investigated risk factors for GC. These pathogens infect more than half of the world's population. Fortunately, only a small fraction of infected individuals develops GC, suggesting high complexity of tumorigenic processes in the human stomach. Recent studies suggest that the multifaceted interplay between microbial, environmental, and host genetic factors underlies gastric tumorigenesis. Many aspects of these interactions still remain unclear. In this review, we update on recent discoveries, focusing on the roles of various gastric pathogens and gastric microbiome in tumorigenesis.
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Affiliation(s)
- Manikandan Palrasu
- Department of Surgery, University of Miami, Miami, FL 33136, USA; (M.P.); (E.Z.); (W.E.-R.)
| | - Elena Zaika
- Department of Surgery, University of Miami, Miami, FL 33136, USA; (M.P.); (E.Z.); (W.E.-R.)
| | - Wael El-Rifai
- Department of Surgery, University of Miami, Miami, FL 33136, USA; (M.P.); (E.Z.); (W.E.-R.)
- Department of Veterans Affairs, Miami VA Healthcare System, Miami, FL 33136, USA
| | - Jianwen Que
- Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA;
| | - Alexander I. Zaika
- Department of Surgery, University of Miami, Miami, FL 33136, USA; (M.P.); (E.Z.); (W.E.-R.)
- Department of Veterans Affairs, Miami VA Healthcare System, Miami, FL 33136, USA
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20
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Yan LR, Lv Z, Jing JJ, Yuan Y, Xu Q. Single nucleotide polymorphisms of whole genes and atrophic gastritis susceptibility:a systematic review and meta-analysis. Gene 2021; 782:145543. [PMID: 33667608 DOI: 10.1016/j.gene.2021.145543] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 01/29/2021] [Accepted: 02/18/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND Atrophic gastritis (AG) is one of the important precancerous lesions of gastric cancer. Single nucleotide polymorphisms (SNPs) are closely related to AG susceptibility. However, the research conclusions on the predictive potential of SNPs are inconsistent. The study aims to retrospect the association between SNPs of whole genes and AG risk by meta-analysis. MATERIALS AND METHODS Up to April 29, 2020, a systematic literature search for the relationship of SNPs with AG susceptibility was performed utilizing PubMed, Web of Science and Chinese National Knowledge Infrastructure. The overall and stratified meta-analyses on extracted data were conducted by Stata11.2. RESULTS 33 case-control studies were enrolled containing 9951 AG patients and 17,252 healthy controls, and 17 SNPs in 12 different genes were systematically reviewed. The results indicated that 12 genes could be categorized based on their functions, including immune response, cell proliferation and apoptosis, and DNA damage repair. For the SNPs in immune response-related genes, the C allele of TLR1 rs4833095 T/C increased AG risk to 1.21-fold and the recessive model of TLR4 rs11536878 in the TLR gene family decreased AG susceptibility to 0.48-fold. The variant alleles of IL-10 rs1800871 (OR = 1.21) and IL-8 rs4073 (OR = 1.22) in the IL gene family were positively associated with AG risk. PSCA rs2294008 enhanced AG risk in all genetic models. SNPs associated with AG susceptibility were mainly focused on immune response-related genes. CONCLUSION These SNPs related to immune response could influence on AG risk and have potential to be AG predictive biomarkers. It is worth noting that the number of studies for each SNPs were insufficient due to the limited published researches and updated meta-analysis needs to be performed based on extensive relevant studies for more reliable results.
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Affiliation(s)
- Li-Rong Yan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang 110001, China
| | - Zhi Lv
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang 110001, China
| | - Jing-Jing Jing
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang 110001, China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang 110001, China.
| | - Qian Xu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang 110001, China.
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21
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Kunze B, Middelhoff M, Maurer HC, Agibalova T, Anand A, Bührer AM, Fang HY, Baumeister T, Steiger K, Strangmann J, Schmid RM, Wang TC, Quante M. Notch signaling drives development of Barrett's metaplasia from Dclk1-positive epithelial tuft cells in the murine gastric mucosa. Sci Rep 2021; 11:4509. [PMID: 33627749 PMCID: PMC7904766 DOI: 10.1038/s41598-021-84011-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 02/08/2021] [Indexed: 12/13/2022] Open
Abstract
Barrett's esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC), but its cellular origin and mechanism of neoplastic progression remain unresolved. Notch signaling, which plays a key role in regulating intestinal stem cell maintenance, has been implicated in a number of cancers. The kinase Dclk1 labels epithelial post-mitotic tuft cells at the squamo-columnar junction (SCJ), and has also been proposed to contribute to epithelial tumor growth. Here, we find that genetic activation of intracellular Notch signaling in epithelial Dclk1-positive tuft cells resulted in the accelerated development of metaplasia and dysplasia in a mouse model of BE (pL2.Dclk1.N2IC mice). In contrast, genetic ablation of Notch receptor 2 in Dclk1-positive cells delayed BE progression (pL2.Dclk1.N2fl mice), and led to increased secretory cell differentiation. The accelerated BE progression in pL2.Dclk1.N2IC mice correlated with changes to the transcriptomic landscape, most notably for the activation of oncogenic, proliferative pathways in BE tissues, in contrast to upregulated Wnt signalling in pL2.Dclk1.N2fl mice. Collectively, our data show that Notch activation in Dclk1-positive tuft cells in the gastric cardia can contribute to BE development.
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Affiliation(s)
- Bettina Kunze
- Klinik und Poliklinik für Innere Medizin II, Technical University of Munich, Munich, Germany
| | - Moritz Middelhoff
- Klinik und Poliklinik für Innere Medizin II, Technical University of Munich, Munich, Germany.
| | - H Carlo Maurer
- Klinik und Poliklinik für Innere Medizin II, Technical University of Munich, Munich, Germany
| | - Tatiana Agibalova
- Klinik und Poliklinik für Innere Medizin II, Technical University of Munich, Munich, Germany
| | - Akanksha Anand
- Klinik und Poliklinik für Innere Medizin II, Technical University of Munich, Munich, Germany
| | - Anne-Marie Bührer
- Klinik und Poliklinik für Innere Medizin II, Technical University of Munich, Munich, Germany
| | - Hsin-Yu Fang
- Klinik und Poliklinik für Innere Medizin II, Technical University of Munich, Munich, Germany
| | - Theresa Baumeister
- Klinik und Poliklinik für Innere Medizin II, Technical University of Munich, Munich, Germany
| | - Katja Steiger
- Institute of Pathology, Technical University of Munich, Munich, Germany
| | - Julia Strangmann
- Klinik und Poliklinik für Innere Medizin II, Technical University of Munich, Munich, Germany
| | - Roland M Schmid
- Klinik und Poliklinik für Innere Medizin II, Technical University of Munich, Munich, Germany
| | - Timothy C Wang
- Department of Medicine, Columbia University Medical Center, New York, NY, USA
| | - Michael Quante
- Klinik und Poliklinik für Innere Medizin II, Technical University of Munich, Munich, Germany. .,Klinik für Innere Medizin II, Gastrointestinale Onkologie, Universitätsklinikum Freiburg, Freiburg, Germany.
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22
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Mallath MK. Gastric Cancer. GERIATRIC GASTROENTEROLOGY 2021:1829-1880. [DOI: 10.1007/978-3-030-30192-7_77] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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23
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Thanaphongdecha P, Karinshak SE, Ittiprasert W, Mann VH, Chamgramol Y, Pairojkul C, Fox JG, Suttiprapa S, Sripa B, Brindley PJ. Infection with Helicobacter pylori Induces Epithelial to Mesenchymal Transition in Human Cholangiocytes. Pathogens 2020; 9:E971. [PMID: 33233485 PMCID: PMC7700263 DOI: 10.3390/pathogens9110971] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Revised: 11/14/2020] [Accepted: 11/18/2020] [Indexed: 02/08/2023] Open
Abstract
Recent reports suggest that the East Asian liver fluke infection, caused by Opisthorchis viverrini, which is implicated in opisthorchiasis-associated cholangiocarcinoma, serves as a reservoir of Helicobacter pylori. The opisthorchiasis-affected cholangiocytes that line the intrahepatic biliary tract are considered to be the cell of origin of this malignancy. Here, we investigated interactions in vitro among human cholangiocytes, Helicobacter pylori strain NCTC 11637, and the congeneric bacillus, Helicobacter bilis. Exposure to increasing numbers of H. pylori at 0, 1, 10, 100 bacilli per cholangiocyte of the H69 cell line induced phenotypic changes including the profusion of thread-like filopodia and a loss of cell-cell contact, in a dose-dependent fashion. In parallel, following exposure to H. pylori, changes were evident in levels of mRNA expression of epithelial to mesenchymal transition (EMT)-encoding factors including snail, slug, vimentin, matrix metalloprotease, zinc finger E-box-binding homeobox, and the cancer stem cell marker CD44. Analysis to quantify cellular proliferation, migration, and invasion in real-time by both H69 cholangiocytes and CC-LP-1 line of cholangiocarcinoma cells using the xCELLigence approach and Matrigel matrix revealed that exposure to 10 H. pylori bacilli per cell stimulated migration and invasion by the cholangiocytes. In addition, 10 bacilli of H. pylori stimulated contact-independent colony establishment in soft agar. These findings support the hypothesis that infection by H. pylori contributes to the malignant transformation of the biliary epithelium.
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Affiliation(s)
- Prissadee Thanaphongdecha
- Research Center for Neglected Tropical Diseases of Poverty, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, DC 20037, USA; (P.T.); (S.E.K.); (W.I.); (V.H.M.)
- Tropical Disease Research Laboratory, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand;
| | - Shannon E. Karinshak
- Research Center for Neglected Tropical Diseases of Poverty, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, DC 20037, USA; (P.T.); (S.E.K.); (W.I.); (V.H.M.)
| | - Wannaporn Ittiprasert
- Research Center for Neglected Tropical Diseases of Poverty, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, DC 20037, USA; (P.T.); (S.E.K.); (W.I.); (V.H.M.)
| | - Victoria H. Mann
- Research Center for Neglected Tropical Diseases of Poverty, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, DC 20037, USA; (P.T.); (S.E.K.); (W.I.); (V.H.M.)
| | - Yaovalux Chamgramol
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; (Y.C.); (C.P.)
| | - Chawalit Pairojkul
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; (Y.C.); (C.P.)
| | - James G. Fox
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA;
| | - Sutas Suttiprapa
- Tropical Disease Research Laboratory, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand;
| | - Banchob Sripa
- Tropical Disease Research Laboratory, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand;
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; (Y.C.); (C.P.)
| | - Paul J. Brindley
- Research Center for Neglected Tropical Diseases of Poverty, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, DC 20037, USA; (P.T.); (S.E.K.); (W.I.); (V.H.M.)
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Efficacy and Gut Dysbiosis of Gentamicin-Intercalated Smectite as a New Therapeutic Agent against Helicobacter pylori in a Mouse Model. Antibiotics (Basel) 2020; 9:antibiotics9080502. [PMID: 32785101 PMCID: PMC7460432 DOI: 10.3390/antibiotics9080502] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/1970] [Revised: 08/07/2020] [Accepted: 08/10/2020] [Indexed: 12/28/2022] Open
Abstract
Helicobacter pylori eradication rate with conventional standard therapy is decreasing owing to antibiotic resistance, necessitating novel antibacterial strategies against H. pylori. We evaluated the efficacy of a gentamicin-intercalated smectite hybrid (S-GM)-based treatment and analyzed fecal microbiome composition in H. pylori-infected mice. To evaluate anti-H. pylori efficacy, mice were divided into eight groups, and H. pylori eradication was assessed by a Campylobacter-like organism (CLO) test and PCR assay of H. pylori in gastric mucosa. One week after H. pylori eradication, pro-inflammatory cytokine levels and atrophic changes in gastric mucosa were examined. Stool specimens were collected and analyzed for microbiome changes. The S-GM-based triple regimen decreased bacterial burden in vivo, compared with that in untreated mice or mice treated with other regimens. The therapeutic reactions in the CLO test from gastric mucosa were both 90% in the standard triple therapy and S-GM therapy group, respectively. Those of H. pylori PCR in mouse gastric mucosa were significantly lower in standard triple therapy and S-GM therapy groups than in the non-treatment group. Toxicity test results showed that S-GM therapy reduced IL-8 level and atrophic changes in gastric mucosa. Stool microbiome analysis revealed that compared with mice treated with the standard triple therapy, mice treated with the S-GM therapy showed microbiome diversity and abundant microorganisms at the phylum level. Our results suggested that S-GM is a promising and effective therapeutic agent against H. pylori infection.
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25
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Kutluana U, Kilciler AG. Is there a possible relationship between gastric intestinal metaplasia and systemic arterial stiffness? REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2020; 111:500-506. [PMID: 31081669 DOI: 10.17235/reed.2019.5945/2018] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND AND AIM Helicobacter pylori (H. pylori) is closely associated with pre-neoplastic lesions such as atrophic gastritis (AG) and gastric intestinal metaplasia (GIM). The relationshionship between inflammation, hyperhomocysteinemia and arterial stiffness is of pathophysiological relevance for the development of cardiovascular disease. This study aimed to investigate the relationship between vitamin B12, folic acid, homocysteine (Hcy) and pulse wave velocity (PWV) levels in patients with GIM, AG and non-atrophic non-metaplastic chronic gastritis. PATIENTS AND METHODS ninety-seven patients with GIM, 67 patients with AG and 69 patients with chronic gastritis were included in the study. Glucose, creatinine, total cholesterol, triglyceride, low-density lipoprotein, cholesterol, high-density lipoprotein cholesterol, vitamin B12, folic acid and Hcy levels were measured by biochemical methods. PWV and other vascular parameters were measured using the Phsyio-port AS device. MAIN RESULTS PWV was higher in patients with GIM and AG than in controls (p < 0.05 and p < 0.05, respectively). Vitamin B12 levels were significantly lower in patients with GIM and AG than in controls (p < 0.01 and p < 0.01, respectively). Folic acid levels were significantly lower in patients with GIM than in controls (p < 0.05). Hcy levels were significantly higher in patients with GIM and AG than in controls (p < 0.001 and p < 0.05, respectively). A logistic regression analysis showed that GIM, AG and vitamin B12 deficiency were predictors for arterial stiffness. CONCLUSIONS PWV values increased in patients with GIM and AG compared to non-atrophic non-metaplastic chronic gastritis, without different conventional cardiovascular risk factors.
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Affiliation(s)
- Ufuk Kutluana
- Gastroenterology, Usak University Faculty of Medicine, Türkiye
| | - Ayse Guldem Kilciler
- Gastroenterology Department, Usak University Faculty of Medicine Usak Education and Research Hospital, TURKEY
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26
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Barber G, Anand A, Katarzyna Oficjalska, Phelan JJ, Heeran AB, Flis E, Clarke NE, Watson JA, Strangmann J, Flood B, O'Neill H, O'Toole D, MacCarthy F, Ravi N, Reynolds JV, Kay EW, Quante M, O'Sullivan J, Creagh EM. Characterizing caspase-1 involvement during esophageal disease progression. Cancer Immunol Immunother 2020; 69:2635-2649. [PMID: 32613271 DOI: 10.1007/s00262-020-02650-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 06/19/2020] [Indexed: 12/16/2022]
Abstract
Barrett's esophagus (BE) is an inflammatory condition and a neoplastic precursor to esophageal adenocarcinoma (EAC). Inflammasome signaling, which contributes to acute and chronic inflammation, results in caspase-1 activation leading to the secretion of IL-1β and IL-18, and inflammatory cell death (pyroptosis). This study aimed to characterize caspase-1 expression, and its functional importance, during disease progression to BE and EAC. Three models of disease progression (Normal-BE-EAC) were employed to profile caspase-1 expression: (1) a human esophageal cell line model; (2) a murine model of BE; and (3) resected tissue from BE-associated EAC patients. BE patient biopsies and murine BE organoids were cultured ex vivo in the presence of a caspase-1 inhibitor, to determine the importance of caspase-1 for inflammatory cytokine and chemokine secretion.Epithelial caspase-1 expression levels were significantly enhanced in BE (p < 0.01). In contrast, stromal caspase-1 levels correlated with histological inflammation scores during disease progression (p < 0.05). Elevated secretion of IL-1β from BE explanted tissue, compared to adjacent normal tissue (p < 0.01), confirmed enhanced activity of caspase-1 in BE tissue. Caspase-1 inhibition in LPS-stimulated murine BE organoids caused a significant reduction in IL-1β (p < 0.01) and CXCL1 (p < 0.05) secretion, confirming the importance of caspase-1 in the production of cytokines and chemokines associated with disease progression from BE to EAC. Targeting caspase-1 activity in BE patients should therefore be tested as a novel strategy to prevent inflammatory complications associated with disease progression.
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Affiliation(s)
- Gillian Barber
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.,Department of Surgery, Trinity Translational Medicine Institute, Trinity College and St. James's Hospital Dublin, Dublin 8, Ireland
| | - Akanksha Anand
- Department of Internal Medicine, Technical University of Munich, Munich, Germany
| | - Katarzyna Oficjalska
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland
| | - James J Phelan
- Department of Surgery, Trinity Translational Medicine Institute, Trinity College and St. James's Hospital Dublin, Dublin 8, Ireland
| | - Aisling B Heeran
- Department of Surgery, Trinity Translational Medicine Institute, Trinity College and St. James's Hospital Dublin, Dublin 8, Ireland
| | - Ewelina Flis
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland
| | - Niamh E Clarke
- Department of Surgery, Trinity Translational Medicine Institute, Trinity College and St. James's Hospital Dublin, Dublin 8, Ireland
| | - Jenny A Watson
- Royal College of Surgeons in Ireland and Beaumont Hospital, Dublin 9, Ireland
| | - Julia Strangmann
- Department of Internal Medicine, Technical University of Munich, Munich, Germany
| | - Brian Flood
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland
| | - Hazel O'Neill
- Department of Surgery, Trinity Translational Medicine Institute, Trinity College and St. James's Hospital Dublin, Dublin 8, Ireland
| | - Dermot O'Toole
- National Oesophageal and Gastric Centre, St. James's Hospital, Dublin 8, Ireland
| | - Finbar MacCarthy
- National Oesophageal and Gastric Centre, St. James's Hospital, Dublin 8, Ireland
| | - Narayanasamy Ravi
- Department of Surgery, Trinity Translational Medicine Institute, Trinity College and St. James's Hospital Dublin, Dublin 8, Ireland.,National Oesophageal and Gastric Centre, St. James's Hospital, Dublin 8, Ireland
| | - John V Reynolds
- Department of Surgery, Trinity Translational Medicine Institute, Trinity College and St. James's Hospital Dublin, Dublin 8, Ireland.,National Oesophageal and Gastric Centre, St. James's Hospital, Dublin 8, Ireland
| | - Elaine W Kay
- Royal College of Surgeons in Ireland and Beaumont Hospital, Dublin 9, Ireland
| | - Michael Quante
- Department of Internal Medicine, Technical University of Munich, Munich, Germany
| | - Jacintha O'Sullivan
- Department of Surgery, Trinity Translational Medicine Institute, Trinity College and St. James's Hospital Dublin, Dublin 8, Ireland.
| | - Emma M Creagh
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
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27
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Ansari S, Yamaoka Y. Role of vacuolating cytotoxin A in Helicobacter pylori infection and its impact on gastric pathogenesis. Expert Rev Anti Infect Ther 2020; 18:987-996. [PMID: 32536287 DOI: 10.1080/14787210.2020.1782739] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Introduction Helicobacter pylori causes, via the influence of several virulence factors, persistent infection of the stomach, which leads to severe complications. Vacuolating cytotoxin A (VacA) is observed in almost all clinical strains of H. pylori; however, only some strains produce the toxigenic and pathogenic VacA, which is influenced by the gene sequence variations. VacA exerts its action by causing cell vacuolation and apoptosis. We performed a PubMed search to review the latest literatures published in English language. Areas covered Articles regarding H. pylori VacA and its genotypes, architecture, internalization, and role in gastric infection and pathogenicity are reviewed. We included the search for recently published literature until January 2020. Expert opinion H. pylori VacA plays a crucial role in severe gastric pathogenicity. In addition, VacA mediated in vivo bacterial survival leads to persistent infection and an enhanced bacterial evasion from the action of antibiotics and the innate host defense system, which leads to drug evasion. VacA as a co-stimulator for the CagA phosphorylation may exert a synergistic effect playing an important role in the CagA-mediated pathogenicity.
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Affiliation(s)
- Shamshul Ansari
- Department of Microbiology, Chitwan Medical College , Bharatpur, Nepal
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine , Yufu, Oita, Japan.,Global Oita Medical Advanced Research Center for Health , Yufu, Oita, Japan.,Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine , Houston, TX, USA.,Borneo Medical and Health Research Centre, Universiti Malaysia Sabah , Kota Kinabaru, Malaysia
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28
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Whary MT, Avenia JMR, Bravo LE, Lofgren JL, Lertpiriyapong K, Mera-Giler R, Piazuelo MB, Correa P, Peek RM, Wilson KT, Fox JG. Contrasting serum biomarker profiles in two Colombian populations with different risks for progression of premalignant gastric lesions during chronic Helicobacter pylori infection. Cancer Epidemiol 2020; 67:101726. [PMID: 32447242 DOI: 10.1016/j.canep.2020.101726] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 04/24/2020] [Accepted: 04/27/2020] [Indexed: 11/26/2022]
Abstract
BACKGROUND Colombians in coastal Tumaco have a lower incidence of Helicobacter pylori-associated gastric cancer compared to individuals from Tuquerres in the high Andes. This is despite nearly universal prevalence of H. pylori infection and chronic gastritis. METHODS H. pylori infection was confirmed by Steiner stain and serology using African and European-origin strains. Gastric histology and serum inflammatory biomarkers in dyspeptic Tumaco or Tuquerres patients were evaluated to predict progression of gastric lesions. RESULTS H. pylori infection was nearly universal by Steiner stain and serology. IgG response to European-origin H. pylori strains were greater than African-origin. High gastric cancer-risk Tuquerres patients, compared to low-risk Tumaco, had significant odds ratios for lesion progression associated with serum IL-5, trefoil factor 3 (TFF3), and low pepsinogen I/II ratio. Sensitivity and specificity for these parameters was 63.8% and 67.9%, respectively, with correctly classifying patients at 66.7%. Most odds ratios for 26 other biomarkers were significant for the town of residency, indicating an environmental impact on Tumaco patients associated with decreased lesion progression. CONCLUSION An IL-5 association with progression of gastric lesions is novel and could be evaluated in addition to TFF3 and pepsinogen I/II ratio as a non-invasive prognostic screen. Results suggest Tumaco patients were exposed to infectious diseases beyond H. pylori such as the documented high incidence of helminthiasis and toxoplasmosis. IMPACT Results support a prior recommendation to evaluate TFF3 and pepsinogen I/II together to predict aggressive gastric histology. Our data indicate IL-5 should be further evaluated as prognostic parameter.
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Affiliation(s)
- Mark T Whary
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA
| | | | - Luis E Bravo
- Department of Pathology, Universidad Del Valle, Cali, Colombia
| | - Jennifer L Lofgren
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Kvin Lertpiriyapong
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Robertino Mera-Giler
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - M Blanca Piazuelo
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Pelayo Correa
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Richard M Peek
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Keith T Wilson
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - James G Fox
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
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Vahid F, Davoodi SH. Nutritional Factors Involved in the Etiology of Gastric Cancer: A Systematic Review. Nutr Cancer 2020; 73:376-390. [PMID: 32336147 DOI: 10.1080/01635581.2020.1756353] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
CONTEXT Since treatment options for GC are limited, the best and most effective way is to try to reduce the incidences and understanding prevention strategies. OBJECTIVE The success in prevention strategies depends on understanding etiologic mechanisms. Our goal is to identify the major nutritional risk factors for GC, and we will examine the controversial evidence. DATA SOURCES We used Pub Med, Google Scholar, Scopus, Science Direct, Elsevier, Springer, and MEDLINE databases for extracting articles. DATA EXTRACTION Human studies published in English from 1997to2018 were included. Two reviewers other than authors initially assessed abstract of 742 papers and 248papers were selected for future assessments. After full review and consideration of the inclusion and exclusion criteria, we used 85 articles. RESULTS Dietary salt is a strong independent risk for GC whereas alcohol is most likely a risk only in the presence of heavy alcohol consumption. Red meat and high-fat diet increase the risk of developing GC but fresh fruits, vegetables and certain micronutrients like selenium and vitamin C are protective. CONCLUSION Some nutrients such as selenium, vitamin C, folate, iron, and zinc are involved in the etiology of GC. On the other hand; salt, fats, alcohol, red meat, and pepper were reported to be risk factors for GC. Since the GC is a heterogeneous malignancy and multiple factors are involved in its genesis.
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Affiliation(s)
- Farhad Vahid
- Department of Nutritional Sciences, School of Health, Arak University of Medical Sciences, Arak, Iran
| | - Sayed Hossein Davoodi
- Faculty of Nutrition Sciences and Food Technology, Department of Nutritional Sciences, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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30
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Fuenmayor-Boscán A, Hernández-Rincón I, Arismendi-Morillo G, Mengual E, Rivero Z, Romero G, Lizarzábal M, Álvarez-Mon M. Changes in the severity of gastric mucosal inflammation associated with Helicobacter pylori in humans coinfected with intestinal helminths. Indian J Gastroenterol 2020; 39:186-195. [PMID: 32436176 DOI: 10.1007/s12664-020-01023-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 02/04/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Though a few studies in animal models suggest that intestinal helminths (IH) favorably affect evolution of gastritis associated with Helicobacter pylori (H. pylori) the studies supporting this concept in humans are only a few and are based on serological data. METHODS To evaluate the possible influence of IH on the human gastric mucosa, three groups of Venezuelan adults with gastropathy (endoscopically diagnosed) were studied: H. pylori-/IH- (n = 17), H. pylori+/IH- (n = 18), and H. pylori+/IH+ (n = 11). Histological analysis (hematoxylin-eosin) and immunohistochemical staining (peroxidase) for cytokines interleukin-1beta (IL-1β), tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), and interleukin 4 (IL-4) were undertaken in gastric antral biopsies. RESULTS Expression of the four cytokines was detected in all individuals in varying degrees, but proinflammatory cytokines were expressed in a higher degree in the H. pylori+/IH- group, mainly IL-1β (Th1-dominant immune response), associated with a higher degree of both histological inflammation and gastric cancer risk index (GCRI), as compared to the H. pylori-/IH- group. In contrast, an increased expression of IL-4 and a reduced expression of proinflammatory cytokines (Th2-dominant response), plus the tendency to a lower degree of mononuclear infiltration, mucosal atrophy in gastric corpus, and GCRI, were evidenced in the coinfected group. CONCLUSIONS The findings of the present study is perhaps the first histological evidence of a possible modulatory effect of IH on the gastric mucosal inflammatory response due to H. pylori infection in humans.
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Affiliation(s)
- Alisbeth Fuenmayor-Boscán
- Departamento de Microbiología, Escuela de Bioanálisis, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela. .,Laboratorio de Bacteriología, Edificio Ciencia y Salud, planta baja, Avenida 18 con calle 65, Apartado Postal 15165, Maracaibo, Venezuela.
| | - Ileana Hernández-Rincón
- Instituto de Investigaciones Biológicas "Doctores Orlando Castejón y Haydée V. Castejón", Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela
| | - Gabriel Arismendi-Morillo
- Instituto de Investigaciones Biológicas "Doctores Orlando Castejón y Haydée V. Castejón", Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela
| | - Edgardo Mengual
- Instituto de Investigaciones Biológicas "Doctores Orlando Castejón y Haydée V. Castejón", Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela
| | - Zulbey Rivero
- Departamento de Microbiología, Escuela de Bioanálisis, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela
| | - Gisela Romero
- Postgrado de Gastroenterología, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela
| | - Maribel Lizarzábal
- Postgrado de Gastroenterología, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela
| | - Melchor Álvarez-Mon
- Laboratorio de Enfermedades del Sistema Inmune y Oncológicas, Departamento de Medicina, Universidad de Alcalá, Madrid, Spain
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31
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Song M, Piazuelo MB, Camargo MC. HTLV-1 infection and health outcomes. THE LANCET. INFECTIOUS DISEASES 2020; 20:406-407. [PMID: 32222205 DOI: 10.1016/s1473-3099(20)30043-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Accepted: 01/17/2020] [Indexed: 10/24/2022]
Affiliation(s)
- Minkyo Song
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA
| | | | - Maria Constanza Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA.
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32
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Zhang X, Arnold IC, Müller A. Mechanisms of persistence, innate immune activation and immunomodulation by the gastric pathogen Helicobacter pylori. Curr Opin Microbiol 2020; 54:1-10. [PMID: 32007716 DOI: 10.1016/j.mib.2020.01.003] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 01/03/2020] [Indexed: 12/20/2022]
Abstract
The gastric bacterium Helicobacter pylori efficiently evades innate immune detection and persistently colonizes its human host. Understanding the genetic determinants that H. pylori uses to establish and maintain persistence, along with their cellular targets, is key to our understanding of the pathogenesis of this extraordinarily successful bacterial colonizer of the human stomach. This review highlights recent advances in elucidating innate immune recognition of H. pylori, its interactions with myeloid cells and the consequences that this very local infection has for immune responses at extragastric sites in models of allergy, autoimmunity and parasitic infection. The human-specific, gram-negative gastric colonizer and carcinogen H. pylori represents the prototype of a persistent bacterial pathogen. It is transmitted during early childhood, typically from mother to infant, and is believed to persist in its human host from the cradle to the grave. The tremendous success of H. pylori in infecting and colonizing half of the world's population, and in continuously accompanying humans since they migrated out of Africa over 60000 years ago, can largely be attributed to its ability to manipulate the host immune system to its own advantage, and to thereby ensure its own persistence and chronicity. In his final years as an active PI, Stanley Falkow increasingly recognized the need to understand bacterial persistence strategies as a prerequisite of understanding the pathogenesis of chronic bacterial infections, and, inspired in large part by Denise Monack's work on Salmonella persistence, many of our discussions at the time revolved around this topic. Multiple labs have since made important contributions to our understanding of innate immune detection of H. pylori, the types and polarization of adaptive immune responses that ensue, the ability of H. pylori to skew such immune responses to its advantage, and its ability to manipulate the host immune system with far-reaching, even systemic consequences. This review attempts to cover some of these topics, with a particular focus on the most recent contributions by researchers in the field.
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Affiliation(s)
- Xiaozhou Zhang
- Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
| | - Isabelle C Arnold
- Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
| | - Anne Müller
- Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
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33
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Olia A, Shimokawa C, Imai T, Suzue K, Hisaeda H. Suppression of systemic lupus erythematosus in NZBWF1 mice infected with Hymenolepis microstoma. Parasitol Int 2020; 76:102057. [PMID: 31954872 DOI: 10.1016/j.parint.2020.102057] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 01/13/2020] [Accepted: 01/14/2020] [Indexed: 12/15/2022]
Abstract
Intestinal helminths induce immune suppressive responses thought to regulate inflammatory diseases including allergies and autoimmune diseases. This study was designed to evaluate whether helminthic infections suppress the natural development of systemic lupus erythematosus (SLE) in NZBWF1 mice. Infection of NZBWF1 SLE-prone mice with two nematodes failed to establish long-lasting settlement. However, the Hymenolepis microstoma (Hm) rodent tapeworm successfully established long-term parasitization of NZBWF1 mice and was used to evaluate the suppressive effects of helminth infection. Ten-month-old NZBWF1 mice developed symptoms including autoantibody generation, proteinuria, glomerular histopathology, and splenomegaly, but mice infected with Hm at 2 months of age did not show any clinical signs. Furthermore, infection with Hm reduced lymphocyte activation and increased regulatory T cells in the spleen and mesenteric lymph nodes. These results indicate that infection with Hm protects NZBWF1 mice from naturally developing SLE and suggest that pathological immunity is attenuated, presumably because of the induction of regulatory T cells.
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Affiliation(s)
- Alex Olia
- Department of Parasitology, Graduate School of Medicine, Gunma University, Gunma, Japan; Department of Parasitology, National Institute of Infectious Diseases, Tokyo, Japan
| | - Chikako Shimokawa
- Department of Parasitology, National Institute of Infectious Diseases, Tokyo, Japan
| | - Takashi Imai
- Department of Parasitology, Graduate School of Medicine, Gunma University, Gunma, Japan
| | - Kazutomo Suzue
- Department of Parasitology, Graduate School of Medicine, Gunma University, Gunma, Japan
| | - Hajime Hisaeda
- Department of Parasitology, Graduate School of Medicine, Gunma University, Gunma, Japan; Department of Parasitology, National Institute of Infectious Diseases, Tokyo, Japan.
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Immunomodulatory effect of Syphacia obvelata in treatment of experimental DSS-induced colitis in mouse model. Sci Rep 2019; 9:19127. [PMID: 31836772 PMCID: PMC6911064 DOI: 10.1038/s41598-019-55552-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 11/29/2019] [Indexed: 02/08/2023] Open
Abstract
The ability of helminth parasite infections to manipulate the immune system of their host towards T regulatory responses has been proposed to suppress the inflammatory response. The aim of this study was to investigate the protective and therapeutic effect of Syphacia obvelata in the treatment of experimental DSS -induced colitis. 50 male C57BL/6 mice were divided into 5 groups: healthy uninfected controls, DSS colitis, receiving only S. obv, preventive (S. obv + DSS) and therapeutic group (DSS + S.obv). Colitis intensity was investigated by measuring body weight changes, stool consistency/bleeding and colon length. To evaluate the immune responses induced by this nematode, TNF-α, IL-10, IL-17, IFN-γ and expressing of FoxP3+ T cells were measured in mesenteric lymph nodes and Peyer’s patches cells. Mice in preventive and therapeutic groups treated with S. obv egg significantly ameliorated the severity of the DSS colitis, indicated by the reduced disease manifestations, improved histopathological scores correlated with the up regulation of Treg responses and down regulation of proinflammatory cytokines. S. obv can prevention and reverse on-going murine DSS colitis. The data suggest that induction of Tregs and change in cytokine profiles during helminthic therapies were responsible for reversed inflammatory events in IBD.
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Tsigalou C, Konstantinidis TG, Cassimos D, Karvelas A, Grapsa A, Tsalkidis A, Panopoulou M, Tsakris A. Inverse association between Helicobacter pylori infection and childhood asthma in Greece: a case-control study. Germs 2019; 9:182-187. [PMID: 32042724 DOI: 10.18683/germs.2019.1174] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 11/06/2019] [Indexed: 12/12/2022]
Abstract
Introduction Helicobacter pylori infection is a well-established etiological factor for a variety of diseases such as peptic ulcer and gastric cancer. On the other hand, there is ongoing research suggesting that H. pylori might have a beneficial effect through a pivotal influence in the immunological response especially in asthma. The aim of the current case-control study was to evaluate the prevalence of H. pylori infection in asthmatic children. Methods Twenty-seven children with exacerbation of persistent asthma, aged 8.6±4.5 years (18 males, 9 females) and 54 age-sex-matched non-asthmatic controls were enrolled. Clinical examination and laboratory investigations were performed. Detection of H. pylori antigen (HpSA) in stool samples was performed by a commercial kit (bioNexia® kit, BioMérieux). Serum specific IgG antibodies were detected by a rapid chromatographic immunoassay (DIAsourceImmunoAssays). Serum IgE concentration was determined by electrochemiluminescence (ECL) (Roche Elecsys) and IgE levels ≥ 90 IU/mL were considered significantly elevated. Results In 3 (11.1%) of the 27 asthmatic children H. pylori infection (based on both detection of HpSA and specific IgG-Abs) was established, whereas as many as 16 of the 54 (29.6%) non-asthmatic ones were found infected (odds ratio 0.1; 95%CI, 0.039-0.305, p=0.026). Conclusions Our findings reveal an inverse relationship between H. pylori infection and children's persistent asthma in Greece.
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Affiliation(s)
- Christina Tsigalou
- MD, PhD Laboratory of Microbiology, School of Medicine, Democritus University of Thrace, Dragana 68100, Alexandroupolis, Greece
| | - Theocharis G Konstantinidis
- MD, PhD Laboratory of Microbiology, School of Medicine, Democritus University of Thrace, Dragana 68100, Alexandroupolis, Greece
| | - Dimitrios Cassimos
- MD, PhD Department of Pediatrics, University General Hospital of Alexandroupolis, Democritus University of Thrace, Dragana 68100, Alexandroupolis, Greece
| | - Alexandros Karvelas
- MD Laboratory of Microbiology, School of Medicine, Democritus University of Thrace, Dragana 68100, Alexandroupolis, Greece
| | - Anastasia Grapsa
- MD Laboratory of Microbiology, School of Medicine, Democritus University of Thrace, Dragana 68100, Alexandroupolis, Greece
| | - Aggelos Tsalkidis
- MD, PhD Department of Pediatrics, University General Hospital of Alexandroupolis, Democritus University of Thrace, Dragana 68100, Alexandroupolis, Greece
| | - Maria Panopoulou
- MD, PhD Laboratory of Microbiology, School of Medicine, Democritus University of Thrace, Dragana 68100, Alexandroupolis, Greece
| | - Athanasios Tsakris
- MD, PhD Laboratory of Microbiology, Medical School, National and Kapodistrian University of Athens, 75 Mikris Asias, Goudi 115 27, Athens, Greece
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Serrano CA, Pierre R, Van Der Pol WJ, Morrow CD, Smith PD, Harris PR. Eradication of Helicobacter pylori in Children Restores the Structure of the Gastric Bacterial Community to That of Noninfected Children. Gastroenterology 2019; 157:1673-1675. [PMID: 31442431 PMCID: PMC6878156 DOI: 10.1053/j.gastro.2019.08.017] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Revised: 08/06/2019] [Accepted: 08/08/2019] [Indexed: 02/08/2023]
Affiliation(s)
- Carolina A. Serrano
- Department of Pediatric Gastroenterology and Nutrition, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | | | - William J. Van Der Pol
- Center for Clinical and Translational Science (Biomedical Informatics), University of Alabama at Birmingham, Birmingham, AL, USA
| | - Casey D. Morrow
- Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Phillip D. Smith
- Department of Medicine (Gastroenterology), University of Alabama at Birmingham, Birmingham, AL, USA
| | - Paul R. Harris
- Department of Pediatric Gastroenterology and Nutrition, Pontificia Universidad Catolica de Chile, Santiago, Chile
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Archampong TN, Asmah RH, Richards CJ, Martin VJ, Bayliss CD, Botão E, David L, Beleza S, Carrilho C. Gastro-duodenal disease in Africa: Literature review and clinical data from Accra, Ghana. World J Gastroenterol 2019; 25:3344-3358. [PMID: 31341360 PMCID: PMC6639557 DOI: 10.3748/wjg.v25.i26.3344] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 05/14/2019] [Accepted: 05/31/2019] [Indexed: 02/06/2023] Open
Abstract
Gastroduodenal disease (GDD) was initially thought to be uncommon in Africa. Amongst others, lack of access to optimal health infrastructure and suspicion of conventional medicine resulted in the reported prevalence of GDD being significantly lower than that in other areas of the world. Following the increasing availability of flexible upper gastro-intestinal endoscopy, it has now become apparent that GDD, especially peptic ulcer disease (PUD), is prevalent across the continent of Africa. Recognised risk factors for gastric cancer (GCA) include Helicobater pylori (H. pylori), diet, Epstein-Barr virus infection and industrial chemical exposure, while those for PUD are H. pylori, non-steroidal anti-inflammatory drug (NSAID)-use, smoking and alcohol consumption. Of these, H. pylori is generally accepted to be causally related to the development of atrophic gastritis (AG), intestinal metaplasia (IM), PUD and distal GCA. Here, we perform a systematic review of the patterns of GDD across Africa obtained with endoscopy, and complement the analysis with new data obtained on pre-malignant gastric his-topathological lesions in Accra, Ghana which was compared with previous data from Maputo, Mozambique. As there is a general lack of structured cohort studies in Africa, we also considered endoscopy-based hospital or tertiary centre studies of symptomatic individuals. In Africa, there is considerable heterogeneity in the prevalence of PUD with no clear geographical patterns. Furthermore, there are differences in PUD within-country despite universally endemic H. pylori infection. PUD is not uncommon in Africa. Most of the African tertiary-centre studies had higher prevalence of PUD when compared with similar studies in western countries. An additional intriguing observation is a recent, ongoing decline in PUD in some African countries where H. pylori infection is still high. One possible reason for the high, sustained prevalence of PUD may be the significant use of NSAIDs in local or over-the-counter preparations. The prevalence of AG and IM, were similar or modestly higher over rates in western countries but lower than those seen in Asia. . In our new data, sampling of 136 patients in Accra detected evidence of pre-malignant lesions (AG and/or IM) in 20 individuals (14.7%). Likewise, the prevalence of pre-malignant lesions, in a sample of 109 patients from Maputo, were 8.3% AG and 8.3% IM. While H. pylori is endemic in Africa, the observed prevalence for GCA is rather low. However, cancer data is drawn from country cancer registries that are not comprehensive due to considerable variation in the availability of efficient local cancer reporting systems, diagnostic health facilities and expertise. Validation of cases and their source as well as specificity of outcome definitions are not explicit in most studies further contributing to uncertainty about the precise incidence rates of GCA on the continent. We conclude that evidence is still lacking to support (or not) the African enigma theory due to inconsistencies in the data that indicate a particularly low incidence of GDD in African countries.
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Affiliation(s)
- Timothy N Archampong
- Department of Medicine and Therapeutics, School of Medicine and Dentistry, University of Ghana, Accra Box 4236, Ghana
- Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, United Kingdom
| | - Richard H Asmah
- Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, University of Ghana, Accra Box 4236, Ghana
| | - Cathy J Richards
- Department of Histopathology, Leicester Royal Infirmary, Leicester LE1 5WW, United Kingdom
| | - Vicki J Martin
- Department of Histopathology, Leicester Royal Infirmary, Leicester LE1 5WW, United Kingdom
| | - Christopher D Bayliss
- Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, United Kingdom
| | - Edília Botão
- Department of Pathology, Maputo Central Hospital, Maputo POBox 1164, Mozambique
| | - Leonor David
- Department of Pathology, Medical Faculty of the University of Porto, Porto 4200-465, Portugal
- Institute of Molecular Pathology and Immunology at the University of Porto (Ipatimup), Porto 4200-465, Portugal
- Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto 4200-465, Portugal
| | - Sandra Beleza
- Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, United Kingdom
| | - Carla Carrilho
- Department of Pathology, Faculty of Medicine, Eduardo Mondlane University, Maputo POBox 257, Mozambique
- Department of Pathology, Maputo Central Hospital, Maputo POBox 1164, Mozambique
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Bhattacharjee S, Mejías-Luque R, Loffredo-Verde E, Toska A, Flossdorf M, Gerhard M, Prazeres da Costa C. Concomitant Infection of S. mansoni and H. pylori Promotes Promiscuity of Antigen-Experienced Cells and Primes the Liver for a Lower Fibrotic Response. Cell Rep 2019; 28:231-244.e5. [DOI: 10.1016/j.celrep.2019.05.108] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 01/29/2019] [Accepted: 05/29/2019] [Indexed: 12/12/2022] Open
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Chard AN, Baker KK, Tsai K, Levy K, Sistrunk JR, Chang HH, Freeman MC. Associations between soil-transmitted helminthiasis and viral, bacterial, and protozoal enteroinfections: a cross-sectional study in rural Laos. Parasit Vectors 2019; 12:216. [PMID: 31064387 PMCID: PMC6505259 DOI: 10.1186/s13071-019-3471-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 04/29/2019] [Indexed: 12/12/2022] Open
Abstract
Background Humans are susceptible to over 1400 pathogens. Co-infection by multiple pathogens is common, and can result in a range of neutral, facilitative, or antagonistic interactions within the host. Soil-transmitted helminths (STH) are powerful immunomodulators, but evidence of the effect of STH infection on the direction and magnitude of concurrent enteric microparasite infections is mixed. Methods We collected fecal samples from 891 randomly selected children and adults in rural Laos. Samples were analyzed for 5 STH species, 6 viruses, 9 bacteria, and 5 protozoa using a quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. We utilized logistic regression, controlling for demographics and household water, sanitation, and hygiene access, to examine the effect of STH infection on concurrent viral, bacterial, and protozoal infection. Results We found that STH infection was associated with lower odds of concurrent viral infection [odds ratio (OR): 0.48, 95% confidence interval (CI): 0.28–0.83], but higher odds of concurrent bacterial infections (OR: 1.81, 95% CI: 1.06–3.07) and concurrent protozoal infections (OR: 1.50, 95% CI: 0.95–2.37). Trends were consistent across STH species. Conclusions The impact of STH on odds of concurrent microparasite co-infection may differ by microparasite taxa, whereby STH infection was negatively associated with viral infections but positively associated with bacterial and protozoal infections. Results suggest that efforts to reduce STH through preventive chemotherapy could have a spillover effect on microparasite infections, though the extent of this impact requires additional study. The associations between STH and concurrent microparasite infection may reflect a reverse effect due to the cross-sectional study design. Additional research is needed to elucidate the exact mechanism of the immunomodulatory effects of STH on concurrent enteric microparasite infection. Electronic supplementary material The online version of this article (10.1186/s13071-019-3471-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Anna N Chard
- Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, 30322, USA
| | - Kelly K Baker
- Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, Iowa, 52242, USA
| | - Kevin Tsai
- Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, Iowa, 52242, USA
| | - Karen Levy
- Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, 30322, USA
| | - Jeticia R Sistrunk
- Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, 30322, USA
| | - Howard H Chang
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, 30322, USA
| | - Matthew C Freeman
- Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, 30322, USA.
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Can neopterin be a useful immune biomarker for differentiating gastric intestinal metaplasia and gastric atrophy from non-atrophic non-metaplastic chronic gastritis? GASTROENTEROLOGIA Y HEPATOLOGIA 2019; 42:289-295. [DOI: 10.1016/j.gastrohep.2019.01.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 12/19/2018] [Accepted: 01/06/2019] [Indexed: 01/10/2023]
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Patrucco F, Venezia L, Gavelli F, Solidoro P. Helicobacter pylori and respiratory diseases: update for pneumologist. ACTA ACUST UNITED AC 2018. [DOI: 10.23736/s0026-4954.18.01824-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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The Rise and Rise of Eosinophilic Gut Diseases Including Eosinophilic Esophagitis Is Probably Not Explained by the Disappearance of Helicobacter pylori, so Who or What's to Blame? Am J Gastroenterol 2018; 113:941-944. [PMID: 29910462 DOI: 10.1038/s41395-018-0125-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 04/30/2018] [Indexed: 02/06/2023]
Abstract
A dramatic increase in eosinophilic esophagitis (EoE) and atopic disease and a dramatic decline in Helicobacter pylori infection has been observed in the last few decades. Previously, it was speculated that the immune response to H. pylori may protect against allergic diseases including EoE, but this study by Molina-Infante et al. shows no clear relationship, and suggests that any correlation is not causal. In truth it is likely that a combination of many factors, including a changing microbiome with increasing hygiene and alterations in early life such as antibiotic exposure, changing diet and other lifestyle factors drive increasing atopic diseases including food allergies and EoE.
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Influence of Helicobacter pylori virulence factors CagA and VacA on pathogenesis of gastrointestinal disorders. Microb Pathog 2018; 117:43-48. [PMID: 29432909 DOI: 10.1016/j.micpath.2018.02.016] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Revised: 01/07/2018] [Accepted: 02/08/2018] [Indexed: 12/23/2022]
Abstract
Helicobacter Pylori (H. pylori) is a gram-negative bacteria infecting numerous people all over the world. It has been established that H. pylori play an important role in pathogenesis of gastritis, peptic ulcer and gastric cancer. Pathogenic features of this bacterium are mainly attributes to the existence of pathogenic islands (PAI) genes. The most known genes in these islands are cytotoxin-associated gene A (CagA) and vacuolating cytotoxin gene (VacA). Most studies demonstrated various frequency of CagA and VacA in patient with peptic ulcer or gastritis in different countries. This variation in CagA and VacA frequency may be due to the capability of this bacterium to be genetically versatile and can alter the expression of these genes with geographic diversity. Although H. pylori infection is not usually associated with any clinical symptoms, but sometimes leads to inflammation in gastrointestinal system and resulted in peptic ulcer and gastric cancer. In this regard, this review will illustrate the importance of Helicobacter pylori in pathogenesis of gastrointestinal disorders with focusing on CagA and VacA virulence factors.
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Bullock KK, Shaffer CL, Brooks AW, Secka O, Forsyth MH, McClain MS, Cover TL. Genetic signatures for Helicobacter pylori strains of West African origin. PLoS One 2017; 12:e0188804. [PMID: 29186206 PMCID: PMC5706691 DOI: 10.1371/journal.pone.0188804] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2017] [Accepted: 11/13/2017] [Indexed: 01/22/2023] Open
Abstract
Helicobacter pylori is a genetically diverse bacterial species that colonizes the stomach in about half of the human population. Most persons colonized by H. pylori remain asymptomatic, but the presence of this organism is a risk factor for gastric cancer. Multiple populations and subpopulations of H. pylori with distinct geographic distributions are recognized. Genetic differences among these populations might be a factor underlying geographic variation in gastric cancer incidence. Relatively little is known about the genomic features of African H. pylori strains compared to other populations of strains. In this study, we first analyzed the genomes of H. pylori strains from seven globally distributed populations or subpopulations and identified encoded proteins that exhibited the highest levels of sequence divergence. These included secreted proteins, an LPS glycosyltransferase, fucosyltransferases, proteins involved in molybdopterin biosynthesis, and Clp protease adaptor (ClpS). Among proteins encoded by the cag pathogenicity island, CagA and CagQ exhibited the highest levels of sequence diversity. We then identified proteins in strains of Western African origin (classified as hspWAfrica by MLST analysis) with sequences that were highly divergent compared to those in other populations of strains. These included ATP-dependent Clp protease, ClpS, and proteins of unknown function. Three of the divergent proteins sequences identified in West African strains were characterized by distinct insertions or deletions up to 8 amino acids in length. These polymorphisms in rapidly evolving proteins represent robust genetic signatures for H. pylori strains of West African origin.
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Affiliation(s)
- Kennady K. Bullock
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
| | - Carrie L. Shaffer
- Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, United States of America
| | - Andrew W. Brooks
- Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
| | - Ousman Secka
- Medical Research Council Unit The Gambia, Banjul, The Gambia
| | - Mark H. Forsyth
- Department of Biology, The College of William and Mary, Williamsburg, Virginia, United States of America
| | - Mark S. McClain
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
| | - Timothy L. Cover
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
- Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, United States of America
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Zhang H, Yue R, Zhao P, Yu X, Li J, Ma G, Tang J, Zhang L, Feng L, Sun L, Song Z, Guo C, Wang N. Proinflammatory follicular helper T cells promote immunoglobulin G secretion, suppress regulatory B cell development, and correlate with worse clinical outcomes in gastric cancer. Tumour Biol 2017. [PMID: 28631561 DOI: 10.1177/1010428317705747] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Gastric cancer is one of the most common and aggressive malignancies. Both bacterial virulence factors and host chronic inflammation are thought to promote gastric cancer development. In this study, we investigated the potential involvement of follicular helper T cells in gastric cancer. Functions of follicular helper T subsets were examined in Helicobacter pylori-infected gastric cancer patients and H. pylori-infected but asymptomatic individuals. We found that the follicular helper T cells in gastric cancer individuals were skewed toward the Th1 and Th17 subsets compared to those in H. pylori-infected but asymptomatic individuals. In a naive B cell-follicular helper T cell coculture, the Th1-follicular helper T cells by themselves were ineffective at stimulating a robust antibody response, unlike the Th2-follicular helper T and Th17-follicular helper T cells. However, Th1-follicular helper T cells significantly promoted the immunoglobulin G response in collaboration with other follicular helper T subsets, through the secretion of interferon gamma. We also found that Th1-follicular helper T cells suppressed the development of interleukin-10+ regulatory B cells, a cell type previously thought to protect H. pylori-infected individuals from tissue damage. In addition, the frequency of Th1-follicular helper T cells in gastric cancer patients was negatively correlated with the disease-free survival of gastric cancer patients after tumor resection. These results suggested that dysregulation of follicular helper T subsets in gastric cancer patients, characterized by increased Th1-follicular helper T cells, contributed to inflammation and tumor development.
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Affiliation(s)
- Hong Zhang
- 1 Department of Hematology & Oncology, The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City, Kaifeng, China
| | - Rongxi Yue
- 1 Department of Hematology & Oncology, The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City, Kaifeng, China
| | - Pengfei Zhao
- 1 Department of Hematology & Oncology, The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City, Kaifeng, China
| | - Xuetao Yu
- 2 Department of Oncology, Tianyou Hospital, Tongji University, Shanghai, China
| | - Junguo Li
- 3 Reproductive Medicine Center, PLA Army General Hospital, Beijing, China
| | - Guoqing Ma
- 1 Department of Hematology & Oncology, The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City, Kaifeng, China
| | - Jiahong Tang
- 1 Department of Hematology & Oncology, The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City, Kaifeng, China
| | - Lixin Zhang
- 1 Department of Hematology & Oncology, The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City, Kaifeng, China
| | - Liying Feng
- 4 Department of Ultrasound, PLA Army General Hospital, Beijing, China
| | - Lidong Sun
- 1 Department of Hematology & Oncology, The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City, Kaifeng, China
| | - Zongchang Song
- 1 Department of Hematology & Oncology, The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City, Kaifeng, China
| | - Chunliang Guo
- 1 Department of Hematology & Oncology, The 155th Central Hospital of PLA/The Key Laboratory of Hematology of Kaifeng City, Kaifeng, China
| | - Ning Wang
- 5 Department of Obstetrics & Gynecology, The 155th Central Hospital of PLA, Kaifeng, China
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Miftahussurur M, Nusi IA, Graham DY, Yamaoka Y. Helicobacter, Hygiene, Atopy, and Asthma. Front Microbiol 2017; 8:1034. [PMID: 28642748 PMCID: PMC5462935 DOI: 10.3389/fmicb.2017.01034] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2016] [Accepted: 05/23/2017] [Indexed: 12/13/2022] Open
Abstract
The hygiene hypothesis links environmental and microbial exposures in early life to the prevalence of atopy, allergy, and asthma. Helicobacter pylori infection is typically acquired in childhood and acquisition of the infection is associated with poor household hygiene. Some population surveys have shown an inverse association between H. pylori infection and atopy, allergy, and asthma leading to the suggestion that H. pylori infection may be protective against disease; others consider it simply a biomarker for poor household hygiene. We review the relevant surveys, cohort studies, meta-analyses, and studies testing the protective hypothesis. Overall, the results of surveys and cohort studies are inconsistent, whereas meta-analyses show a significant but weak inverse correlation. In contrast, studies directly testing the protection hypothesis in relation to asthma in populations with poor hygiene and low H. pylori prevalence failed to confirm a protective effect. H. pylori is a major cause of human disease including chronic gastritis, peptic ulcer, and gastric malignancies. H. pylori infections most likely serve as a biomarker for poor hygienic conditions in childhood. We conclude that while synergistic interactions between environmental factors in childhood are important determinants of the pathogenesis of atopy, allergy, and asthma; H. pylori is inversely related to good hygiene and thus it's presence serves as a biomarker rather than for a specific prevention role for H. pylori or H. pylori antigens.
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Affiliation(s)
- Muhammad Miftahussurur
- Gastroenterology and Hepatology Section, Department of Medicine, Baylor College of MedicineHouston, TX, United States
- Department of Environmental and Preventive Medicine, Oita University Faculty of MedicineYufu, Japan
- Gastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine-Institute of Tropical Disease, Universitas AirlanggaSurabaya, Indonesia
| | - Iswan A. Nusi
- Gastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine-Institute of Tropical Disease, Universitas AirlanggaSurabaya, Indonesia
| | - David Y. Graham
- Gastroenterology and Hepatology Section, Department of Medicine, Baylor College of MedicineHouston, TX, United States
| | - Yoshio Yamaoka
- Gastroenterology and Hepatology Section, Department of Medicine, Baylor College of MedicineHouston, TX, United States
- Department of Environmental and Preventive Medicine, Oita University Faculty of MedicineYufu, Japan
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Attenuation of Helicobacter pylori-induced gastric inflammation by prior cag- strain (AM1) infection in C57BL/6 mice. Gut Pathog 2017; 9:14. [PMID: 28286572 PMCID: PMC5343599 DOI: 10.1186/s13099-017-0161-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Accepted: 02/28/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Helicobacter pylori, colonize in stomach of ~50% of the world population. cag pathogenicity Island of H. pylori is one of the important virulent factors that attributed to gastric inflammation. Coinfection with H. pylori strain with different genetic makeup alters the degree of pathogenicity and susceptibility towards antibiotics. The present study investigates host immunomodulatory effects of H. pylori infection by both cag+ strain (SS1) and cag- strain (AM1). C57BL/6 mice were infected with AM1 or SS1 strain as well as AM1 followed by SS1 (AM1/SS1) and vice versa. RESULTS Mice infected with AM1/SS1 strain exhibited less gastric inflammation and reduced proMMP9 and proMMP3 activities in gastric tissues as compared to SS1/SS1 and SS1/AM1 infected groups. The expression of both MMP9 and MMP3 followed similar trend like activity in infected tissues. Both Th1 and Th17 responses were induced by SS1 strain more profoundly than AM1 strain infection which induced solely Th1 response in spleen and gastric tissues. Moreover, IFN-γ, TNF-α, IL-1β and IL-12 were significantly downregulated in mice spleen and gastric tissues infected by AM1/SS1 compared to SS1/SS1 but not with SS1/AM1 coinfection. Surprisingly, IL-17 level was dampened significantly in AM1/SS1 compared to SS1/AM1 coinfected groups. Furthermore, number of Foxp3+ T-regulatory (Treg) cells and immunosuppressive cytokines like IL-10 and TGF-β were reduced in AM1/SS1 compared to SS1/SS1 and SS1/AM1 coinfected mice gastric tissues. CONCLUSIONS These data suggested that prior H. pylori cag- strain infection attenuated the severity of gastric pathology induced by subsequent cag+ strain in C57BL/6 mice. Prior AM1 infection induced Th1 cytokine IFN-γ, which reduced the Th17 response induced by subsequent SS1 infection. The reduced gastritis in AM1/SS1-infected mice might also be due to enrichment of AM1- primed Treg cells in the gastric compartment which inhibit Th1 and Th17 responses to subsequent SS1 infection. In summary, prior infection by non-virulent H. pylori strain (AM1) causes reduction of subsequent virulent strain (SS1) infection by regulation of inflammatory cytokines and MMPs expression.
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Bagheri V, Memar B, Momtazi AA, Sahebkar A, Gholamin M, Abbaszadegan MR. Cytokine networks and their association with Helicobacter pylori infection in gastric carcinoma. J Cell Physiol 2017; 233:2791-2803. [PMID: 28121015 DOI: 10.1002/jcp.25822] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Accepted: 12/16/2016] [Indexed: 12/20/2022]
Abstract
Cytokine networks as dynamic networks are pivotal aspects of tumor immunology, especially in gastric cancer (GC), in which infection, inflammation, and antitumor immunity are key elements of disease progression. In this review, we describe functional roles of well-known GC-modulatory cytokines, highlight the functions of cytokines with more recently described roles in GC, and emphasize the therapeutic potential of targeting the complex cytokine milieu. We also focus on the role of Helicobacter pylori (HP)-induced inflammation in GC and discuss how HP-induced chronic inflammation can lead to the induction of stem cell hyperplasia, morphological changes in gastric mucosa and GC development.
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Affiliation(s)
- Vahid Bagheri
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Human Genetic Division, Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Bahram Memar
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Pathology, Faculty of Medicine, Emam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Abbas Momtazi
- Department of Medical Biotechnology, Student Research Committee, Nanotechnology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mehran Gholamin
- Human Genetic Division, Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Reza Abbaszadegan
- Human Genetic Division, Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Godkin A, Smith KA. Chronic infections with viruses or parasites: breaking bad to make good. Immunology 2017; 150:389-396. [PMID: 28009488 PMCID: PMC5343343 DOI: 10.1111/imm.12703] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2016] [Revised: 12/02/2016] [Accepted: 12/16/2016] [Indexed: 12/19/2022] Open
Abstract
Eukaryotic forms of life have been continually invaded by microbes and larger multicellular parasites, such as helminths. Over a billion years ago bacterial endosymbionts permanently colonized eukaryotic cells leading to recognized organelles with a distinct genetic lineage, such as mitochondria and chloroplasts. Colonization of our skin and mucosal surfaces with bacterial commensals is now known to be important for host health. However, the contribution of chronic virus and parasitic infections to immune homeostasis is being increasingly questioned. Persistent infection does not necessarily equate to exhibiting a chronic illness: healthy hosts (e.g. humans) have chronic viral and parasitic infections with no evidence of disease. Indeed, there are now examples of complex interactions between these microbes and hosts that seem to confer an advantage to the host at a particular time, suggesting that the relationship has progressed along an axis from parasitic to commensal to one of a mutualistic symbiosis. This concept is explored using examples from viruses and parasites, considering how the relationships may be not only detrimental but also beneficial to the human host.
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Affiliation(s)
- Andrew Godkin
- Division of Infection and Immunity, Cardiff University, Cardiff, Glamorgan, UK
| | - Katherine A Smith
- Division of Infection and Immunity, Cardiff University, Cardiff, Glamorgan, UK
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