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

Romain Bouziat; Reinhard Hinterleitner; Judy J. Brown; Jennifer E. Stencel-Baerenwald; Mine Ikizler; Toufic Mayassi; Marlies Meisel; Sangman M. Kim; Valentina Discepolo; Andrea J. Pruijssers; Jordan D. Ernest; Jason A. Iskarpatyoti; Léa M.M. Costes; Ian Lawrence; Brad A. Palanski; Mukund Varma; Matthew A. Zurenski; Solomiia Khomandiak; Nicole McAllister; Pavithra Aravamudhan; Karl W. Boehme; Fengling Hu; Janneke N. Samsom; Hans Christian Reinecker; Sonia S. Kupfer; Stefano Guandalini; Carol E. Semrad; Valérie Abadie; Chaitan Khosla; Luis B. Barreiro; Ramnik J. Xavier; Aylwin Ng; Terence S. Dermody; Bana Jabri

doi:10.1126/science.aah5298

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

Romain Bouziat, Reinhard Hinterleitner, Judy J. Brown, Jennifer E. Stencel-Baerenwald, Mine Ikizler, Toufic Mayassi, Marlies Meisel, Sangman M. Kim, Valentina Discepolo, Andrea J. Pruijssers, Jordan D. Ernest, Jason A. Iskarpatyoti, Léa M.M. Costes, Ian Lawrence, Brad A. Palanski, Mukund Varma, Matthew A. Zurenski, Solomiia Khomandiak, Nicole McAllister, Pavithra AravamudhanKarl W. Boehme, Fengling Hu, Janneke N. Samsom, Hans Christian Reinecker, Sonia S. Kupfer, Stefano Guandalini, Carol E. Semrad, Valérie Abadie, Chaitan Khosla, Luis B. Barreiro, Ramnik J. Xavier, Aylwin Ng, Terence S. Dermody, Bana Jabri

Research output: Contribution to journal › Article › peer-review

318 Scopus citations

Abstract

Viral infections have been proposed to elicit pathological processes leading to the initiation of T helper 1 (T_H1) 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 (pT_reg) conversion and promoting T_H1 immunity to dietary antigen. Initiation of T_H1 immunity to dietary antigen was dependent on interferon regulatory factor 1 and dissociated from suppression of pT_reg 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.

Original language	English (US)
Pages (from-to)	44-50
Number of pages	7
Journal	Science
Volume	356
Issue number	6333
DOIs	https://doi.org/10.1126/science.aah5298
State	Published - Apr 7 2017
Externally published	Yes

ASJC Scopus subject areas

General

Access to Document

10.1126/science.aah5298

Cite this

Bouziat, R., Hinterleitner, R., Brown, J. J., Stencel-Baerenwald, J. E., Ikizler, M., Mayassi, T., Meisel, M., Kim, S. M., Discepolo, V., Pruijssers, A. J., Ernest, J. D., Iskarpatyoti, J. A., Costes, L. M. M., Lawrence, I., Palanski, B. A., Varma, M., Zurenski, M. A., Khomandiak, S., McAllister, N., ... Jabri, B. (2017). Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease. Science, 356(6333), 44-50. https://doi.org/10.1126/science.aah5298

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, LMM, 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 2017, 'Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease', Science, vol. 356, no. 6333, pp. 44-50. https://doi.org/10.1126/science.aah5298

@article{db6f543ce1074176b2275b56c747fc99,

title = "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.",

author = "Romain Bouziat and Reinhard Hinterleitner and Brown, {Judy J.} and Stencel-Baerenwald, {Jennifer E.} and Mine Ikizler and Toufic Mayassi and Marlies Meisel and Kim, {Sangman M.} and Valentina Discepolo and Pruijssers, {Andrea J.} and Ernest, {Jordan D.} and Iskarpatyoti, {Jason A.} and Costes, {L{\'e}a M.M.} and Ian Lawrence and Palanski, {Brad A.} and Mukund Varma and Zurenski, {Matthew A.} and Solomiia Khomandiak and Nicole McAllister and Pavithra Aravamudhan and Boehme, {Karl W.} and Fengling Hu and Samsom, {Janneke N.} and Reinecker, {Hans Christian} and Kupfer, {Sonia S.} and Stefano Guandalini and Semrad, {Carol E.} and Val{\'e}rie Abadie and Chaitan Khosla and Barreiro, {Luis B.} and Xavier, {Ramnik J.} and Aylwin Ng and Dermody, {Terence S.} and Bana Jabri",

year = "2017",

month = apr,

day = "7",

doi = "10.1126/science.aah5298",

language = "English (US)",

volume = "356",

pages = "44--50",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6333",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=85017383204&partnerID=8YFLogxK

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

SN - 0036-8075

VL - 356

SP - 44

EP - 50

JO - Science

JF - Science

IS - 6333

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this