Innate Immune Pathways in Virus-Induced Autoimmune Diabetes

We recently hypothesized that Toll-like receptor-induced innate upregulation by Kilham rat virus (KRV) in the BioBreeding diabetes-resistant (BBDR) rat model plays a key role in the mechanism of diabetes induction. To address this hypothesis, we analyzed innate immune signaling pathways upregulated by KRV in vitro and in vivo. We demonstrate that KRV activates the signal transducer and activator of transcription (STAT)-l in spleen cells in vitro and that this activation can be blocked by TLR9 inhibition. We also show that KRV upregulates STAT-1 in pancreatic lymph nodes early after virus infection. Our data may implicate TLR9-induced STAT-1 signaling pathways in KRV-induced innate immune activation in the BBDR rat and raise the possibility that these pathways are involved in mediating autoimmune diabetes.