De Nardo Dominic
Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3050, Australia.
Cytokine. 2015 Aug;74(2):181-9. doi: 10.1016/j.cyto.2015.02.025. Epub 2015 Apr 3.
Families of innate immune receptors serve as the bodies primary defence system by recognising and rapidly responding to infection by microorganisms or to endogenous danger signals and initiating inflammatory processes. Whilst Toll-like receptors (TLRs) were the first family to be discovered, important and exciting discoveries continue to emerge into the molecular mechanisms that control their activation and regulation. Herein, I will provide an overview of TLR activation and their downstream signalling cascades, and discuss some of the recent findings concerning the assembly of a TLR oligomeric signalling platform, known as the Myddosome. Further, a brief examination of the importance of crosstalk between multiple TLRs or between TLRs and other innate immune receptors for appropriate and coordinated immune responses will be presented. Finally, I will discuss the importance of mechanisms that regulate TLRs with a focus on the role of activating transcription factor 3 (ATF3) in modulating transcriptional responses downstream of TLRs.
先天性免疫受体家族通过识别并快速响应微生物感染或内源性危险信号,并启动炎症过程,从而充当机体的主要防御系统。虽然Toll样受体(TLR)是最早被发现的家族,但关于控制其激活和调节的分子机制,重要且令人兴奋的发现仍不断涌现。在此,我将概述TLR的激活及其下游信号级联反应,并讨论一些关于被称为Myddosome的TLR寡聚信号平台组装的最新发现。此外,还将简要探讨多个TLR之间或TLR与其他先天性免疫受体之间的相互作用对于适当且协调的免疫反应的重要性。最后,我将讨论调节TLR的机制的重要性,重点关注激活转录因子3(ATF3)在调节TLR下游转录反应中的作用。