Double-Stranded RNA Induces Pancreatic -Cell Apoptosis by Activation of the Toll-Like Receptor

OBJECTIVE—Viral infections contribute to the pathogenesis of type 1 diabetes. Viruses, or viral products such as double-stranded RNA (dsRNA), affect pancreatic -cell survival and trigger autoimmunity by unknown mechanisms. We presently investigated the mediators and downstream effectors of dsRNA-induced -cell death. RESEARCH DESIGN AND METHODS—Primary rat -cells and islet cells from wild-type, toll-like receptor (TLR) 3, type I interferon receptor (IFNAR1), or interferon regulatory factor (IRF)-3 knockout mice were exposed to external dsRNA (exter-nal polyinosinic-polycytidylic acid [PICex]) or were transfected with dsRNA ([PICin]). RESULTS—TLR3 signaling mediated PICex-induced nuclear factor-B (NF-B) and IRF-3 activation and -cell apoptosis. PICin activated NF-B and IRF-3 in a TLR3-independent manner