Sen Ganes C, Sarkar Saumendra N
Department of Molecular Genetics/NC20, The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Cytokine Growth Factor Rev. 2005 Feb;16(1):1-14. doi: 10.1016/j.cytogfr.2005.01.006.
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.
哺乳动物的Toll样受体可识别入侵微生物的成分，并触发由大量细胞基因转录诱导介导的先天免疫反应的第一线。Toll样受体3（TLR3）被认为是细胞对病毒感染反应的主要介质，因为它对双链（ds）RNA有反应，而双链RNA是病毒复制的常见副产物。本文重点关注由TLR3和dsRNA激活的信号通路的性质。由TLR3激活诱导的基因包括那些编码分泌型抗病毒细胞因子（如干扰素（IFN））的基因，以及那些编码细胞内病毒应激诱导蛋白的基因。最近的研究揭示了TLR3信号传导的几个独特特征，在此予以强调。具体而言，我们讨论了受体酪氨酸磷酸化、PI3激酶以及转录因子IRF-3和NF-κB的两步激活在介导TLR3信号传导中的作用。
