Tartey Sarang, Takeuchi Osamu
a Laboratory of Infection and Prevention, Institute for Virus Research, Kyoto University , Kawara-Cho, Sakyo-Ku, Kyoto , Japan.
b AMED-CREST, Japan Agency for Medical Research and Development , Kyoto , Japan.
Int Rev Immunol. 2017 Mar 4;36(2):57-73. doi: 10.1080/08830185.2016.1261318. Epub 2017 Jan 6.
The innate immune system deploys a variety of pattern-recognition receptors (PRRs) which include Toll-like receptors (TLRs), RIG-I-like receptors, NOD-like receptors, and C-type lectin receptors to detect the invasion of pathogens and initiate protective responses. The intercellular and intracellular orchestration of signals from different PRRs, their endogenous or microbial ligands and accessory molecules determine the stimulatory or inhibitory responses. Progressing over the last two decades, considerable research on the molecular mechanisms underlying host-pathogen interactions has led to a paradigm shift of our understanding of TLR signaling in the innate immune system. Given that a significant amount of evidence implicates TLRs in the pathogenesis of immune diseases and cancer, and their activation occurs early in the inflammatory cascade, they are attractive targets for novel therapeutic agents. In this review, we discuss the recent advances in TLR signaling cross talks and the mechanism of pathogen recognition with special emphasis on the role of TLRs in tumor immunity and TLR-targeted therapeutics.
先天性免疫系统部署了多种模式识别受体（PRR），包括 Toll 样受体（TLR）、维甲酸诱导基因 I 样受体、NOD 样受体和 C 型凝集素受体，以检测病原体的入侵并启动保护性反应。来自不同 PRR、其内源或微生物配体及辅助分子的细胞间和细胞内信号协调决定了刺激或抑制反应。在过去二十年中，对宿主-病原体相互作用潜在分子机制的大量研究导致了我们对先天性免疫系统中 TLR 信号传导理解的范式转变。鉴于大量证据表明 TLR 参与免疫疾病和癌症的发病机制，且它们的激活在炎症级联反应早期发生，因此它们是新型治疗药物的有吸引力的靶点。在本综述中，我们讨论 TLR 信号传导相互作用的最新进展以及病原体识别机制，特别强调 TLR 在肿瘤免疫中的作用和 TLR 靶向治疗。
