| Literature DB >> 28386004 |
Romain Bouziat1,2, Reinhard Hinterleitner1,2, Judy J Brown3,4, Jennifer E Stencel-Baerenwald3,4, Mine Ikizler4,5, Toufic Mayassi1,2, Marlies Meisel1,2, Sangman M Kim1,2, Valentina Discepolo1,6, Andrea J Pruijssers4,5, Jordan D Ernest1,2, Jason A Iskarpatyoti4,5, Léa M M Costes1,7, Ian Lawrence1,2, Brad A Palanski8, Mukund Varma9,10, Matthew A Zurenski1,2, Solomiia Khomandiak4,5, Nicole McAllister3,4, Pavithra Aravamudhan4,5, Karl W Boehme4,5, Fengling Hu1, Janneke N Samsom7, Hans-Christian Reinecker9, Sonia S Kupfer1,11, Stefano Guandalini11,12, Carol E Semrad1,11, Valérie Abadie13, Chaitan Khosla8,14,15, Luis B Barreiro16, Ramnik J Xavier9,10,17, Aylwin Ng9,10, Terence S Dermody18,4,5,19,20, Bana Jabri21,2,11,12,22.
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.Entities:
Mesh：
Substances：
Year: 2017 PMID： 28386004 PMCID： PMC5506690 DOI： 10.1126/science.aah5298
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728