Akira Shizuo, Sato Shintaro
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Scand J Infect Dis. 2003;35(9):555-62. doi: 10.1080/00365540310015683.
Toll-like receptors (TLRs) play a crucial role in the recognition of invading pathogens and the activation of subsequent immune responses against them. Individual TLRs recognize distinct pathogen-associated molecular patterns (PAMPs). The TLR family harbors an extracellular leucine-rich repeat (LRR) domain as well as a cytoplasmic domain that is homologous to that of interleukin-1 receptor (IL-1R). Upon stimulation, TLR recruits IL-1R-associated protein kinases via adaptor MyD88, and finally induces activation of nuclear factor-kappaB and mitogen-activated protein kinases. However, the response to TLR ligands varies, indicating the diversity of TLR signaling pathways. Besides MyD88, several novel adaptor molecules have recently been identified. Differential utilization of these adaptor molecules may provide the specificity in the TLR signaling. Characterization of each TLR signaling pathway will reveal the molecular mechanism of self-tolerance as well as cross-tolerance in response to a variety of PAMPs.
Toll样受体（TLRs）在识别入侵病原体以及激活随后针对这些病原体的免疫反应中发挥着关键作用。单个TLR识别不同的病原体相关分子模式（PAMPs）。TLR家族包含一个细胞外富含亮氨酸重复序列（LRR）结构域以及一个与白细胞介素-1受体（IL-1R）的细胞质结构域同源的结构域。受到刺激后，TLR通过接头分子MyD88招募IL-1R相关蛋白激酶，最终诱导核因子-κB和丝裂原活化蛋白激酶的激活。然而，对TLR配体的反应各不相同，这表明TLR信号通路具有多样性。除了MyD88，最近还鉴定出了几种新型接头分子。这些接头分子的不同利用可能为TLR信号传导提供特异性。对每个TLR信号通路的表征将揭示自身耐受以及对多种PAMPs的交叉耐受的分子机制。
