Takeda Kiyoshi, Akira Shizuo
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, ERATO, Japan Science and Technology Corporation, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
J Dermatol Sci. 2004 Apr;34(2):73-82. doi: 10.1016/j.jdermsci.2003.10.002.
Toll-like receptors (TLRs) sense invasion of microorganisms by detecting microbial components that are conserved among pathogens. Recognition of microbial components by TLRs triggers activation of the innate immune system. Signaling pathways via TLRs originate from conserved cytoplasmic Toll/IL-1 receptor (TIR) domains. Recent accumulating evidence demonstrates that TIR domain-containing adaptors, such as MyD88, TIRAP/Mal, TRIF, and TRAM, regulate TLR-mediated signaling pathways. MyD88 is common to all TLR-mediated pathways, which lead to the production of inflammatory cytokines, whereas TRIF mediates induction of IFN-beta in TLR3 and TLR4 signaling pathways. TIRAP/Mal is implicated in the TLR2- and TLR4-mediated MyD88-dependent signaling pathway. TRAM is specifically involved in the TLR4-mediated TRIF-dependent pathway. Thus, TIR domain-containing adaptors play a pivotal role in TLR signaling pathways, which culminate in pathogen-specific immune responses.
Toll样受体（TLRs）通过检测病原体中保守的微生物成分来感知微生物的入侵。TLRs对微生物成分的识别会触发先天免疫系统的激活。通过TLRs的信号通路起源于保守的细胞质Toll/IL-1受体（TIR）结构域。最近越来越多的证据表明，含TIR结构域的衔接蛋白，如MyD88、TIRAP/Mal、TRIF和TRAM，调节TLR介导的信号通路。MyD88存在于所有TLR介导的通路中，这些通路会导致炎性细胞因子的产生，而TRIF在TLR3和TLR4信号通路中介导IFN-β的诱导。TIRAP/Mal参与TLR2和TLR4介导的MyD88依赖性信号通路。TRAM特异性参与TLR4介导的TRIF依赖性通路。因此，含TIR结构域的衔接蛋白在TLR信号通路中起关键作用，这些信号通路最终导致针对病原体的特异性免疫反应。
