*Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan.
Biochem J. 2014 Mar 1;458(2):195-201. doi: 10.1042/BJ20131492.
The innate immune system recognizes pathogen- and damage-associated molecular patterns using pattern-recognition receptors that activate a wide range of signalling cascades to maintain host homoeostasis against infection and inflammation. Endosomal TLR3 (Toll-like receptor 3), a type I transmembrane protein, senses RNAs derived from cells with viral infection or sterile tissue damage, leading to the induction of type I interferon and cytokine production, as well as dendritic cell maturation. It has been accepted that TLR3 recognizes perfect dsRNA, but little has been addressed experimentally with regard to the structural features of virus- or host-derived RNAs that activate TLR3. Recently, a TLR3 agonist was identified, which was a virus-derived 'structured' RNA with incomplete stem structures. Both dsRNA and structured RNA are similarly internalized through clathrin- and raftlin-dependent endocytosis and delivered to endosomal TLR3. The dsRNA uptake machinery, in addition to TLR3, is critical for extracellular viral RNA-induced immune responses. A wide spectrum of TLR3 ligand structures beyond dsRNA and their delivery systems provide new insights into the physiological role of TLR3 in virus- or host-derived RNA-induced immune responses. In the present paper, we focus on the system for extracellular recognition of RNA and its delivery to TLR3.
先天免疫系统使用模式识别受体识别病原体和损伤相关的分子模式，激活广泛的信号级联反应，以维持宿主对感染和炎症的体内平衡。内体 TLR3（Toll 样受体 3）是一种 I 型跨膜蛋白，可感知来自病毒感染或无菌组织损伤的细胞衍生的 RNA，导致 I 型干扰素和细胞因子的产生以及树突状细胞的成熟。人们已经接受 TLR3 识别完美的 dsRNA，但关于激活 TLR3 的病毒或宿主衍生 RNA 的结构特征，实验研究甚少。最近，鉴定出一种 TLR3 激动剂，它是一种具有不完全茎结构的病毒衍生的“结构”RNA。dsRNA 和结构 RNA 都通过网格蛋白和筏蛋白依赖性内吞作用被类似地内化，并递送至内体 TLR3。dsRNA 摄取机制除了 TLR3 之外，对于细胞外病毒 RNA 诱导的免疫反应也是至关重要的。dsRNA 以外的广泛 TLR3 配体结构及其递药系统为 TLR3 在病毒或宿主衍生 RNA 诱导的免疫反应中的生理作用提供了新的见解。在本文中，我们重点介绍细胞外 RNA 的识别系统及其向 TLR3 的递呈。
