Akira Shizuo, Hoshino Katuaki
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and SORST of Japan Science and Technology, Osaka, Japan.
J Infect Dis. 2003 Jun 15;187 Suppl 2:S356-63. doi: 10.1086/374749.
Toll-like receptors (TLRs) play an essential role in the detection of invading pathogens in the body. Individual TLRs recognize distinct components derived from pathogens, which is followed by cytokine production. The TLR family harbors extracellular leucine-rich repeat domains and a cytoplasmic domain that is homologous to that of the interleukin (IL)-1 receptor (IL-1R) family. After stimulation, TLR recruits IL-1R-associated kinase via adaptor myeloid differentiation factor 88 (MyD88) and induces activation of NF-kappaB and mitogen-activated protein kinases. Cytokine production in response to each TLR ligand is completely abrogated in MyD88-deficient cells, which indicates that MyD88 is an essential shared signaling molecule in the IL-1R/Toll family. The TLR4 signal has an MyD88-independent pathway that is involved in induction of type I interferons (IFNs) and IFN-inducible genes via IFN regulatory factor-3 activation. A recently identified adaptor molecule, Toll-IL receptor domain-containing adaptor protein/MyD88 adaptor-like, may participate in the MyD88-independent pathway.
Toll样受体（TLRs）在机体检测入侵病原体的过程中发挥着至关重要的作用。单个TLR可识别病原体衍生的不同成分，随后产生细胞因子。TLR家族含有细胞外富含亮氨酸的重复结构域以及与白细胞介素（IL）-1受体（IL-1R）家族同源的胞质结构域。受到刺激后，TLR通过衔接蛋白髓样分化因子88（MyD88）募集IL-1R相关激酶，并诱导核因子κB和丝裂原活化蛋白激酶的激活。在MyD88缺陷细胞中，对每种TLR配体的细胞因子产生完全被消除，这表明MyD88是IL-1R/Toll家族中一种必需的共享信号分子。TLR4信号具有一条不依赖MyD88的途径，该途径通过激活干扰素调节因子-3参与I型干扰素（IFNs）和IFN诱导基因的诱导。最近鉴定出的一种衔接分子，含Toll-IL受体结构域的衔接蛋白/MyD88样衔接蛋白，可能参与不依赖MyD88的途径。
