1. Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease
- Author
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Mine R. Ikizler, Fengling Hu, Matthew A. Zurenski, Bana Jabri, Karl W. Boehme, Hans Christian Reinecker, Chaitan Khosla, Brad A. Palanski, Sangman M. Kim, Romain Bouziat, Jason A. Iskarpatyoti, Valentina Discepolo, Ian Lawrence, Jordan D. Ernest, Léa M.M. Costes, Valérie Abadie, Mukund Varma, Janneke N. Samsom, Terence S. Dermody, Solomiia Khomandiak, Ramnik J. Xavier, Carol E. Semrad, Marlies Meisel, Andrea J. Pruijssers, Jennifer E. Stencel-Baerenwald, Nicole McAllister, Sonia S. Kupfer, Reinhard Hinterleitner, Toufic Mayassi, Pavithra Aravamudhan, Stefano Guandalini, Luis B. Barreiro, Judy J. Brown, Aylwin Ng, 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., Aravamudhan, P., Boehme, K. W., Hu, F., Samsom, J. N., Reinecker, H. -C., Kupfer, S. S., Guandalini, S., Semrad, C. E., Abadie, V., Khosla, C., Barreiro, L. B., Xavier, R. J., Ng, A., Dermody, T. S., Jabri, B., and Pediatrics
- Subjects
0301 basic medicine ,viruses ,Autoimmunity ,Receptor, Interferon alpha-beta ,Disease ,Mice ,0302 clinical medicine ,Interferon ,Reoviridae Infection ,Pathogen ,Multidisciplinary ,Effector ,Intestine ,Intestines ,medicine.anatomical_structure ,Antigen ,Interferon Type I ,030211 gastroenterology & hepatology ,Genetic Engineering ,Human ,medicine.drug ,Glutens ,Regulatory T cell ,Mice, Transgenic ,Biology ,Reoviridae ,Article ,Virus ,03 medical and health sciences ,Immunity ,Immune Tolerance ,medicine ,Animals ,Humans ,Antigens ,Autoantibodies ,Inflammation ,Transglutaminases ,Animal ,Th1 Cells ,biochemical phenomena, metabolism, and nutrition ,Virology ,Diet ,Reoviridae Infections ,Mice, Inbred C57BL ,Celiac Disease ,Disease Models, Animal ,030104 developmental biology ,IRF1 ,Immunology ,Gluten ,Interferon Regulatory Factor-1 - 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.
- Published
- 2017
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