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Science. 2017 Apr 7;356(6333):44-50. doi: 10.1126/science.aah5298.

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

Author information

1
Department of Medicine, University of Chicago, Chicago, IL, USA.
2
Committee on Immunology, University of Chicago, Chicago, IL, USA.
3
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
4
Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, TN, USA.
5
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
6
Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, and CeInGe-Biotecnologie Avanzate, Naples, Italy.
7
Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center Rotterdam-Sophia Children's Hospital, Rotterdam, Netherlands.
8
Department of Chemistry, Stanford University, Stanford, CA, USA.
9
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.
10
Broad Institute of MIT and Harvard University, Cambridge, MA, USA.
11
University of Chicago Celiac Disease Center, University of Chicago, Chicago, IL, USA.
12
Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL, USA.
13
Department of Microbiology, Infectiology, and Immunology, University of Montreal, and the Centre Hospitalier Universitaire (CHU) Sainte-Justine Research Center, Montreal, Quebec, Canada.
14
Department of Chemical Engineering, Stanford University, Stanford, CA, USA.
15
Stanford ChEM-H, Stanford University, Stanford, California, USA.
16
Department of Genetics, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada.
17
Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
18
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. bjabri@bsd.uchicago.edu terence.dermody@chp.edu.
19
Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
20
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
21
Department of Medicine, University of Chicago, Chicago, IL, USA. bjabri@bsd.uchicago.edu terence.dermody@chp.edu.
22
Department of Pathology, University of Chicago, Chicago, IL, USA.

Abstract

Viral infections have been proposed to elicit pathological processes leading to the initiation of T helper 1 (TH1) 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 (pTreg) conversion and promoting TH1 immunity to dietary antigen. Initiation of TH1 immunity to dietary antigen was dependent on interferon regulatory factor 1 and dissociated from suppression of pTreg 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.

PMID:
28386004
PMCID:
PMC5506690
DOI:
10.1126/science.aah5298
[Indexed for MEDLINE]
Free PMC Article

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