Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
Trends Immunol. 2012 Sep;33(9):449-58. doi: 10.1016/j.it.2012.05.002. Epub 2012 Jun 20.
Toll-like receptors (TLRs) sense invading microbial pathogens and play crucial roles in the activation of innate and adaptive immunity. However, excessive TLR activation can disrupt immune homeostasis, and may be responsible for the development of autoimmune and inflammatory diseases. As such, the molecules and pathways that negatively control TLR signaling have been intensively investigated. Here, we discuss recent insights into the negative regulation of TLR signaling, with focus on three major mechanisms: (i) dissociation of adaptor complexes; (ii) degradation of signal proteins; and (iii) transcriptional regulation. We also highlight how pathogens negatively target TLR signaling as a strategy to evade the host immune response.
toll 样受体（TLRs）可感知入侵的微生物病原体，并在先天和适应性免疫的激活中发挥关键作用。然而，TLR 的过度激活会破坏免疫稳态，并可能导致自身免疫和炎症性疾病的发生。因此，负调控 TLR 信号的分子和途径受到了广泛研究。在此，我们讨论了 TLR 信号负调控的最新研究进展，重点介绍了三种主要机制：（i）衔接蛋白复合物的解离；（ii）信号蛋白的降解；和（iii）转录调控。我们还强调了病原体如何通过负向靶向 TLR 信号作为一种逃避宿主免疫反应的策略。
