Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
J Leukoc Biol. 2019 Feb;105(2):339-351. doi: 10.1002/JLB.MR0318-096R. Epub 2018 Sep 26.
TLRs are expressed on the plasma and endosomal membranes of innate immune cells acting as sensors of foreign and inherent danger signals that threaten the host. Upon activation, TLRs facilitate the assembly of large intracellular oligomeric signaling complexes, termed Myddosomes, which initiate key signal transduction pathways to elicit critical inflammatory immune responses. The formation of the Myddosome is integral for TLR signaling; however, the molecular mechanisms controlling its formation, disassembly, and the subsequent proximal signaling events remain to be clearly defined. In this review, we present a brief overview of TLR signal transduction pathways, summarize the current understanding of the Myddosome and the proteins that comprise its structure, including MyD88 and members of the IL-1 receptor-associated kinase (IRAK) family. Finally, we will discuss recent advances and open questions regarding early TLR signaling in the context of the Myddosome complex.
TLRs 表达于先天免疫细胞的质膜和内体膜上，作为识别威胁宿主的外来和固有危险信号的传感器。在激活后，TLRs 促进大型细胞内寡聚信号复合物的组装，称为 Myddosomes，其引发关键信号转导途径以引发关键的炎症免疫反应。Myddosome 的形成对于 TLR 信号转导至关重要；然而，控制其形成、解体以及随后的近端信号事件的分子机制仍有待明确界定。在这篇综述中，我们简要概述了 TLR 信号转导途径，总结了当前对 Myddosome 及其结构蛋白的理解，包括 MyD88 和 IL-1 受体相关激酶 (IRAK) 家族成员。最后，我们将讨论关于 Myddosome 复合物中 TLR 信号早期的最新进展和开放性问题。
