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


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.

SUBMITTER: Bouziat R 

PROVIDER: S-EPMC5506690 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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

Bouziat Romain R   Hinterleitner Reinhard R   Brown Judy J JJ   Stencel-Baerenwald Jennifer E JE   Ikizler Mine M   Mayassi Toufic T   Meisel Marlies M   Kim Sangman M SM   Discepolo Valentina V   Pruijssers Andrea J AJ   Ernest Jordan D JD   Iskarpatyoti Jason A JA   Costes Léa M M LM   Lawrence Ian I   Palanski Brad A BA   Varma Mukund M   Zurenski Matthew A MA   Khomandiak Solomiia S   McAllister Nicole N   McAllister Nicole N   Aravamudhan Pavithra P   Boehme Karl W KW   Hu Fengling F   Samsom Janneke N JN   Reinecker Hans-Christian HC   Kupfer Sonia S SS   Guandalini Stefano S   Semrad Carol E CE   Abadie Valérie V   Khosla Chaitan C   Barreiro Luis B LB   Xavier Ramnik J RJ   Ng Aylwin A   Dermody Terence S TS   Jabri Bana B  

Science (New York, N.Y.) 20170401 6333


Viral infections have been proposed to elicit pathological processes leading to the initiation of T helper 1 (T<sub>H</sub>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 elic  ...[more]

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