Celiac.com 04/17/2017 - A team of researchers recently set out to test this hypothesis and to gain insights into mechanisms underlying virus-induced loss of tolerance to dietary antigens. To do so, they developed a viral infection model that makes use of two reovirus strains that infect the intestine, but which differ in their immunopathological outcomes.
Reoviruses usually infect humans and mice without overt physical symptoms. Prior research by Bouziat et al., has shown that immune responses to two gut-infecting reoviruses take different paths in mice, as noted in the Perspective by Verdu and Caminero.
Both reoviruses triggered protective immune responses. However, when one of the reoviruses occurred in the presence of a dietary antigen, such as gluten or ovalbumin, tolerance to the dietary antigen disappeared. This was because this strain blocked the formation of tolerogenic T cells. Instead, it promoted T helper 1 immunity to the dietary antigen through interferon regulatory factor 1 signaling. Moreover, celiac disease patients also showed elevated levels of antibodies against reovirus.
Reovirus is an avirulent pathogen that elicits protective immunity, but these researcher have shown that it can also cause a disruption of 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. TH1 immunity to dietary antigen depended on interferon regulatory factor 1, and was unconnected to suppression of pTreg conversion, which was mediated by type-1 interferon.
This study provides important scientific support for the idea that this seemingly mild reovirus plays a major role in the development of celiac disease.
Clearly further study is needed to determine the exact nature of the role of reovirus in celiac disease, and to determine if these connections might prompt any changes in celiac diagnosis and treatment.
The researchers are variously affiliated with the Department of Medicine, the Department of Pathology, and the Committee on Immunology at the University of Chicago in Chicago, IL, USA; the Department of Pathology, Microbiology, and Immunology, the Department of Pediatrics, and the Elizabeth B. Lamb Center for Pediatric Research at Vanderbilt University Medical Center in Nashville, TN, USA; the Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, and CeInGe–Biotecnologie Avanzate, Naples, Italy; the Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center Rotterdam-Sophia Children’s Hospital, Rotterdam, Netherlands; the Department of Chemistry, Stanford University, Stanford, CA, USA; the Division of Gastroenterology, Department of Medicine, Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; the Broad Institute of MIT and Harvard University, Cambridge, MA, USA; the University of Chicago Celiac Disease Center at the University of Chicago, Chicago, IL, USA; the Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL, USA; the Department of Microbiology, Infectiology, and Immunology, University of Montreal, and the Centre Hospitalier Universitaire (CHU) Sainte-Justine Research Center, Montreal, Quebec, Canada; the Department of Chemical Engineering, Stanford University, Stanford, CA, USA; the Stanford ChEM-H, Stanford University, Stanford, California, USA; the Department of Genetics, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada; the Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; the Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; and the Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.