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Publication
Reovirus infection triggers inflammatory responses to dietary antigens and
development of celiac disease.
Authors Bouziat R, Hinterleitner R, Brown JJ, Stencel-Baerenwald JE, Ikizler M, Mayassi
T, Meisel M, Kim SM, Discepolo V, Pruijssers AJ, Ernest JD, Iskarpatyoti JA,
Costes LM, Lawrence I, Palanski BA, Varma M, Zurenski MA, Khomandiak S,
McAllister N, Aravamudhan P, Boehme KW, Hu F, Samsom JN, Reinecker HC, Kupfer
SS, Guandalini S, Semrad CE, Abadie V, Khosla C, Barreiro LB, Xavier RJ, Ng A,
Dermody TS, Jabri B
Submitted By Submitted Externally on 7/27/2017
Status Published
Journal Science (New York, N.Y.)
Year 2017
Date Published 4/1/2017
Volume : Pages 356 : 44 - 50
PubMed Reference 28386004
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.




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