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

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.