Model of reovirus strain-specific induction of celiac disease.
Following peroral inoculation, reovirus T1L and T3D-RV infect the intestine. T3D-RV causes caspase-3 activation and intestinal epithelial cell sloughing, which subsequently leads to rapid viral clearance. T1L, however, subverts these antiviral responses to establish prolonged infection, triggering release of type 1 interferons and other virus response factors (yet to be defined) that induce IRF-1 expression in lamina propria dendritic cells. In the context of this inflammatory cytokine milieu, dendritic cells phagocytose new food antigen (such as gluten), traffic to the mesenteric lymph nodes, and secrete IRF-1–induced IL-12 to activate gluten-specific inflammatory T cells (TH1). Type 1 interferons up-regulated during T1L infection also inhibit regulatory T cells, leading to expansion of TH1 immunity to gluten in the development of celiac disease. IRF-1, interferon regulatory factor-1; TH1, gluten-specific inflammatory T cells.
