Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease.

Autor: Bouziat R; Department of Medicine, University of Chicago, Chicago, IL, USA.; Committee on Immunology, University of Chicago, Chicago, IL, USA., Hinterleitner R; Department of Medicine, University of Chicago, Chicago, IL, USA.; Committee on Immunology, University of Chicago, Chicago, IL, USA., Brown JJ; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, TN, USA., Stencel-Baerenwald JE; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, TN, USA., Ikizler M; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA., Mayassi T; Department of Medicine, University of Chicago, Chicago, IL, USA.; Committee on Immunology, University of Chicago, Chicago, IL, USA., Meisel M; Department of Medicine, University of Chicago, Chicago, IL, USA.; Committee on Immunology, University of Chicago, Chicago, IL, USA., Kim SM; Department of Medicine, University of Chicago, Chicago, IL, USA.; Committee on Immunology, University of Chicago, Chicago, IL, USA., Discepolo V; Department of Medicine, University of Chicago, Chicago, IL, USA.; Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, and CeInGe-Biotecnologie Avanzate, Naples, Italy., Pruijssers AJ; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA., Ernest JD; Department of Medicine, University of Chicago, Chicago, IL, USA.; Committee on Immunology, University of Chicago, Chicago, IL, USA., Iskarpatyoti JA; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA., Costes LM; Department of Medicine, University of Chicago, Chicago, IL, USA.; Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center Rotterdam-Sophia Children's Hospital, Rotterdam, Netherlands., Lawrence I; Department of Medicine, University of Chicago, Chicago, IL, USA.; Committee on Immunology, University of Chicago, Chicago, IL, USA., Palanski BA; Department of Chemistry, Stanford University, Stanford, CA, USA., Varma M; Division of Gastroenterology, Department of Medicine, Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard University, Cambridge, MA, USA., Zurenski MA; Department of Medicine, University of Chicago, Chicago, IL, USA.; Committee on Immunology, University of Chicago, Chicago, IL, USA., Khomandiak S; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA., McAllister N; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, TN, USA., Aravamudhan P; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA., Boehme KW; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA., Hu F; Department of Medicine, University of Chicago, Chicago, IL, USA., Samsom JN; Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center Rotterdam-Sophia Children's Hospital, Rotterdam, Netherlands., Reinecker HC; Division of Gastroenterology, Department of Medicine, Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Kupfer SS; Department of Medicine, University of Chicago, Chicago, IL, USA.; University of Chicago Celiac Disease Center, University of Chicago, Chicago, IL, USA., Guandalini S; University of Chicago Celiac Disease Center, University of Chicago, Chicago, IL, USA.; Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL, USA., Semrad CE; Department of Medicine, University of Chicago, Chicago, IL, USA.; University of Chicago Celiac Disease Center, University of Chicago, Chicago, IL, USA., Abadie V; Department of Microbiology, Infectiology, and Immunology, University of Montreal, and the Centre Hospitalier Universitaire (CHU) Sainte-Justine Research Center, Montreal, Quebec, Canada., Khosla C; Department of Chemistry, Stanford University, Stanford, CA, USA.; Department of Chemical Engineering, Stanford University, Stanford, CA, USA.; Stanford ChEM-H, Stanford University, Stanford, California, USA., Barreiro LB; Department of Genetics, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada., Xavier RJ; Division of Gastroenterology, Department of Medicine, Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard University, Cambridge, MA, USA.; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Ng A; Division of Gastroenterology, Department of Medicine, Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard University, Cambridge, MA, USA., Dermody TS; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. bjabri@bsd.uchicago.edu terence.dermody@chp.edu.; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Jabri B; Department of Medicine, University of Chicago, Chicago, IL, USA. bjabri@bsd.uchicago.edu terence.dermody@chp.edu.; Committee on Immunology, University of Chicago, Chicago, IL, USA.; University of Chicago Celiac Disease Center, University of Chicago, Chicago, IL, USA.; Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL, USA.; Department of Pathology, University of Chicago, Chicago, IL, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2017 Apr 07; Vol. 356 (6333), pp. 44-50.
DOI: 10.1126/science.aah5298
Abstrakt: Viral infections have been proposed to elicit pathological processes leading to the initiation of T helper 1 (T H 1) immunity against dietary gluten and celiac disease (CeD). To test this hypothesis and gain insights into mechanisms underlying virus-induced loss of tolerance to dietary antigens, we developed a viral infection model that makes use of two reovirus strains that infect the intestine but differ in their immunopathological outcomes. Reovirus is an avirulent pathogen that elicits protective immunity, but we discovered that it can nonetheless disrupt intestinal immune homeostasis at inductive and effector sites of oral tolerance by suppressing peripheral regulatory T cell (pT reg ) conversion and promoting T H 1 immunity to dietary antigen. Initiation of T H 1 immunity to dietary antigen was dependent on interferon regulatory factor 1 and dissociated from suppression of pT reg conversion, which was mediated by type-1 interferon. Last, our study in humans supports a role for infection with reovirus, a seemingly innocuous virus, in triggering the development of CeD.
(Copyright © 2017, American Association for the Advancement of Science.)
Databáze: MEDLINE
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