Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 1730, Lineu Prestes Avenue, São Paulo, SP, 05508-000, Brazil,
Arch Immunol Ther Exp (Warsz). 2013 Dec;61(6):427-43. doi: 10.1007/s00005-013-0243-0. Epub 2013 Sep 22.
Toll-like receptors (TLRs) sense microbial products and play an important role in innate immunity. Currently, 11 members of TLRs have been identified in humans, with important function in host defense in early steps of the inflammatory response. TLRs are present in the plasma membrane (TLR1, TLR2, TLR4, TLR5, TLR6) and endosome (TLR3, TLR7, TLR8, TLR9) of leukocytes. TLRs and IL-1R are a family of receptors related to the innate immune response that contain an intracellular domain known as the Toll-IL-1R (TIR) domain that recruits the TIR-containing cytosolic adapters MyD88, TRIF, TIRAP and TRAM. The classical pathway results in the activation of both nuclear factor κB and MAPKs via the IRAK complex, with two active kinases (IRAK-1 and IRAK-4) and two non-catalytic subunits (IRAK-2 and IRAK-3/M). The classical pro-inflammatory TLR signaling pathway leads to the synthesis of inflammatory cytokines and chemokines, such as IL-1β, IL-6, IL-8, IL-12 and TNF-α. In humans, genetic defects have been identified that impair signaling of the TLR pathway and this may result in recurrent pyogenic infections, as well as virus and fungi infections. In this review, we discuss the main mechanisms of microbial recognition and the defects involving TLRs.
Toll 样受体（TLRs）识别微生物产物，在先天免疫中发挥重要作用。目前，人类已鉴定出 11 种 TLRs，在炎症反应的早期阶段对宿主防御具有重要功能。TLRs 存在于白细胞的质膜（TLR1、TLR2、TLR4、TLR5、TLR6）和内体（TLR3、TLR7、TLR8、TLR9）中。TLRs 和 IL-1R 是与先天免疫反应相关的受体家族，包含一个称为 Toll-IL-1R（TIR）结构域的细胞内结构域，该结构域招募含有 TIR 的胞质衔接蛋白 MyD88、TRIF、TIRAP 和 TRAM。经典途径通过 IRAK 复合物激活核因子 κB 和 MAPKs，其中包含两个活性激酶（IRAK-1 和 IRAK-4）和两个非催化亚基（IRAK-2 和 IRAK-3/M）。经典的促炎 TLR 信号通路导致炎症细胞因子和趋化因子的合成，如 IL-1β、IL-6、IL-8、IL-12 和 TNF-α。在人类中，已经鉴定出了一些遗传缺陷，这些缺陷会损害 TLR 途径的信号转导，这可能导致复发性化脓性感染，以及病毒和真菌感染。在这篇综述中，我们讨论了微生物识别的主要机制和涉及 TLR 的缺陷。
