Transcriptional signaling by double-stranded RNA: role of TLR3.

Mammalian Toll-like receptors recognize components of invading microbes and trigger the first line of innate immune response that is mediated by transcriptional induction of a large number of cellular genes. Toll-like receptor 3 (TLR3) is thought to be a major mediator of cellular response to viral infection, because it responds to double-stranded (ds) RNA, a common by-product of viral replication. This article is focused on the nature of the signaling pathways activated by TLR3 and dsRNA. The genes induced by TLR3 activation include those that encode secreted antiviral cytokines, such as interferon (IFN), and those that encode intracellular viral stress-inducible proteins. Recent studies have revealed several unique features of TLR3 signaling that are highlighted here. Specifically, we discuss the roles of receptor tyrosine phosphorylation, PI3 kinase and two-step activation of the transcription factors, IRF-3 and NF-kappaB, in mediating TLR3-signaling.