Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease.
Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease.
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DOI：
10.1126/science.aah5298
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发表时间：
2017-04-07
期刊：
影响因子：
--
通讯作者：
Jabri B
中科院分区：
文献类型：
--
作者：
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
病毒感染可诱导T辅助细胞1(TH1)对膳食面筋蛋白和乳糜泻(CED)的免疫。为了验证这一假设并深入了解病毒导致对饮食抗原失去耐受性的潜在机制，我们开发了一个病毒感染模型，该模型利用了两种呼肠孤病毒株，这两种呼肠孤病毒株感染肠道，但免疫病理结果不同。呼肠孤病毒是一种无毒的病原体，可诱导保护性免疫，但我们发现它仍可通过抑制外周调节性T细胞(PTreg)的转换和促进TH1对饮食抗原的免疫来破坏口服耐受的诱导和效应部位的肠道免疫稳态。TH1对饮食抗原的免疫启动依赖于干扰素调节因子1，与抑制pTreg转换无关，pTreg转换是由1型干扰素介导的。最后，我们对人类的研究支持呼肠孤病毒感染在触发CED发展中的作用。呼肠孤病毒是一种看似无害的病毒。
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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