TY - JOUR
T1 - Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease
AU - Bouziat, Romain
AU - Hinterleitner, Reinhard
AU - Brown, Judy J.
AU - Stencel-Baerenwald, Jennifer E.
AU - Ikizler, Mine
AU - Mayassi, Toufic
AU - Meisel, Marlies
AU - Kim, Sangman M.
AU - Discepolo, Valentina
AU - Pruijssers, Andrea J.
AU - Ernest, Jordan D.
AU - Iskarpatyoti, Jason A.
AU - Costes, Léa M.M.
AU - Lawrence, Ian
AU - Palanski, Brad A.
AU - Varma, Mukund
AU - Zurenski, Matthew A.
AU - Khomandiak, Solomiia
AU - McAllister, Nicole
AU - Aravamudhan, Pavithra
AU - Boehme, Karl W.
AU - Hu, Fengling
AU - Samsom, Janneke N.
AU - Reinecker, Hans Christian
AU - Kupfer, Sonia S.
AU - Guandalini, Stefano
AU - Semrad, Carol E.
AU - Abadie, Valérie
AU - Khosla, Chaitan
AU - Barreiro, Luis B.
AU - Xavier, Ramnik J.
AU - Ng, Aylwin
AU - Dermody, Terence S.
AU - Jabri, Bana
PY - 2017/4/7
Y1 - 2017/4/7
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85017383204&partnerID=8YFLogxK
U2 - 10.1126/science.aah5298
DO - 10.1126/science.aah5298
M3 - Article
C2 - 28386004
AN - SCOPUS:85017383204
VL - 356
SP - 44
EP - 50
JO - Science
JF - Science
SN - 0036-8075
IS - 6333
ER -