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

被引：345

作者：

Bouziat, Romain ^{[1
,2
]}

Hinterleitner, Reinhard ^{[1
,2
]}

Brown, Judy J. ^{[3
,4
]}

Stencel-Baerenwald, Jennifer E. ^{[3
,4
]}

Ikizler, Mine ^{[4
,5
]}

Mayassi, Toufic ^{[1
,2
]}

Meisel, Marlies ^{[1
,2
]}

Kim, Sangman M. ^{[1
,2
]}

Discepolo, Valentina ^{[1
,6
]}

Pruijssers, Andrea J. ^{[4
,5
]}

Ernest, Jordan D. ^{[1
,2
]}

Iskarpatyoti, Jason A. ^{[4
,5
]}

Costes, Lea M. M. ^{[1
,7
]}

Lawrence, Ian ^{[1
,2
]}

Palanski, Brad A. ^{[8
]}

Varma, Mukund ^{[9
,10
,11
,12
,13
]}

Zurenski, Matthew A. ^{[1
,2
]}

Khomandiak, Solomiia ^{[4
,5
]}

McAllister, Nicole ^{[3
,4
]}

Aravamudhan, Pavithra ^{[4
,5
]}

Boehme, Karl W. ^{[4
,5
]}

Hu, Fengling ^{[1
]}

Samsom, Janneke N. ^{[7
]}

Reinecker, Hans-Christian ^{[9
,10
,11
]}

Kupfer, Sonia S. ^{[1
]}

Guandalini, Stefano ^{[14
,15
]}

Semrad, Carol E. ^{[1
,14
]}

Abadie, Valerie ^{[16
,17
]}

Khosla, Chaitan ^{[18
,19
]}

Barreiro, Luis B. ^{[20
]}

Xavier, Ramnik J. ^{[9
,10
,11
,12
,13
,21
,22
]}

Ng, Aylwin ^{[9
,10
,11
,12
,13
]}

Dermody, Terence S. ^{[3
,4
,5
,23
,24
]}

Jabri, Bana ^{[1
,2
,14
,15
,25
]}

机构：

[1] Univ Chicago, Dept Med, Chicago, IL USA

[2] Univ Chicago, Comm Immunol, Chicago, IL USA

[3] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN USA

[4] Vanderbilt Univ, Med Ctr, Elizabeth B Lamb Ctr Pediat Res, Nashville, TN USA

[5] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN USA

[6] Univ Naples Federico II, CeInGe Biotecnol Avanzate, Dept Translat Med Sci, Sect Pediat, Naples, Italy

[7] Erasmus Univ, Rotterdam Sophia Childrens Hosp, Med Ctr, Div Gastroenterol & Nutr,Lab Pediat, Rotterdam, Netherlands

[8] Stanford Univ, Dept Chem, Stanford, CA USA

[9] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Gastrointestinal Unit, Boston, MA USA

[10] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA USA

[11] Harvard Med Sch, Boston, MA USA

[12] Harvard Univ, Cambridge, MA 02138 USA

[13] MIT, Broad Inst, Cambridge, MA 02138 USA

[14] Univ Chicago, Celiac Dis Ctr, Chicago, IL USA

[15] Univ Chicago, Dept Pediat, Sect Gastroenterol Hepatol & Nutr, Chicago, IL USA

[16] Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ, Canada

[17] Ctr Hosp Univ CHU, St Justine Res Ctr, Montreal, PQ, Canada

[18] Stanford Univ, Dept Chem Engn, Stanford, CA USA

[19] Stanford Univ, Stanford ChEM H, Stanford, CA USA

[20] CHU St Justine Res Ctr, Dept Genet, Montreal, PQ, Canada

[21] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA USA

[22] Harvard Med Sch, Boston, MA USA

[23] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA USA

[24] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA USA

[25] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA

来源：

SCIENCE | 2017年 / 356卷 / 6333期

基金：

美国国家卫生研究院; 奥地利科学基金会;

关键词：

REGULATORY FACTOR-I; CLASSICAL DENDRITIC CELLS; IMMUNE-RESPONSES; NATURAL-HISTORY; ORAL TOLERANCE; T-CELLS; CHILDREN; MICE; EXPRESSION; TISSUE;

D O I：

10.1126/science.aah5298

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：44 / +

页数：7

共 46 条

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