Matsumoto Misako, Funami Kenji, Tatematsu Megumi, Azuma Masahiro, Seya Tsukasa
Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan.
Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan.
Methods Enzymol. 2014;535:149-65. doi: 10.1016/B978-0-12-397925-4.00010-9.
The innate immune system plays key roles in antimicrobial responses by developing the pattern-recognition receptors that recognize microbial components. The endosomal Toll-like receptors (TLRs) and cytosolic RIG-I-like receptors (RLRs) both recognize viral nucleic acids and are essential for antiviral immunity. Recent evidence suggests that compartmentalization of the receptors, and also their adaptor molecule, is important for discrimination between self and nonself and for distinct innate immune signals. TLR3 is a type I transmembrane protein that localizes in the endosomal membrane in myeloid dendritic cells (DCs) and fibroblasts/epithelial cells. TLR3 recognizes extracellular viral double-stranded RNA (dsRNA) and the synthetic dsRNA, poly(I:C). On recognition of dsRNA in the endosomes, TLR3 oligomerizes and induces type I interferon and proinflammatory cytokine production via an adaptor molecule, TICAM-1 (also known as TRIF). Additionally, the TLR3 signal in DCs triggers gene transcription required for DC maturation and the activation of natural killer cells and cytotoxic T lymphocytes. Remarkably, it has been reported that extracellular dsRNA is also recognized by cytosolic RLR. Making a distinction between TLR3-mediated endosomal signaling and RLR-mediated signaling is key to understanding the role of these receptors in innate immunity.
先天性免疫系统通过开发识别微生物成分的模式识别受体，在抗菌反应中发挥关键作用。内体 Toll 样受体（TLR）和胞质视黄酸诱导基因 I 样受体（RLR）都能识别病毒核酸，并且对于抗病毒免疫至关重要。最近的证据表明，这些受体及其衔接分子的区室化对于区分自我和非自我以及产生不同的先天性免疫信号很重要。TLR3 是一种 I 型跨膜蛋白，定位于髓样树突状细胞（DC）和成纤维细胞/上皮细胞的内体膜中。TLR3 识别细胞外病毒双链 RNA（dsRNA）和合成的 dsRNA 聚肌胞苷酸（poly(I:C)）。在内体中识别 dsRNA 后，TLR3 会寡聚化，并通过衔接分子 TICAM-1（也称为 TRIF）诱导 I 型干扰素和促炎细胞因子的产生。此外，DC 中的 TLR3 信号会触发 DC 成熟以及自然杀伤细胞和细胞毒性 T 淋巴细胞激活所需的基因转录。值得注意的是，据报道细胞外 dsRNA 也可被胞质 RLR 识别。区分 TLR3 介导的内体信号传导和 RLR 介导的信号传导是理解这些受体在先天性免疫中作用的关键。
