Honko Anna N, Mizel Steven B
Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Immunol Res. 2005;33(1):83-101. doi: 10.1385/IR:33:1:083.
Flagella are locomotive organelles present on a wide range of bacteria and are important for the pathogenesis of many species. Cells of the innate immune system lack memory per se, but recognize conserved pathogen-associated molecular patterns (PAMPs) through a family of type I membrane receptors known as Toll-like receptors (TLRs). Flagellin, the major structural component of flagella, is a highly conserved protein recognized in hosts by TLR5. Signaling of flagellin via TLR5/TLR4 heteromeric complexes enhances the diversity of the response, likely by engaging MyD88-independent adaptors to activate the interferon pathway. Flagellin is a potent immune activator, stimulating diverse biologic effects that mediate both innate inflammatory responses as well as the development of adaptive immunity. Binding of flagellin to the extracellular domain of TLR5 rapidly induces a signal cascade that culminates in the production of proinflammatory mediators such as cytokines, chemokines, and costimulatory molecules. This review focuses on the mechanisms of action of flagellin and its effects on both innate and adaptive immunity.
鞭毛是存在于多种细菌上的运动细胞器，对许多物种的致病性很重要。先天免疫系统的细胞本身缺乏记忆，但通过一类称为Toll样受体（TLR）的I型膜受体识别保守的病原体相关分子模式（PAMP）。鞭毛蛋白是鞭毛的主要结构成分，是一种在宿主中被TLR5识别的高度保守的蛋白质。鞭毛蛋白通过TLR5/TLR4异源复合物发出信号，可能通过激活MyD88非依赖性衔接蛋白来激活干扰素途径，从而增强反应的多样性。鞭毛蛋白是一种强大的免疫激活剂，可刺激多种生物学效应，介导先天炎症反应以及适应性免疫的发展。鞭毛蛋白与TLR5的细胞外结构域结合会迅速诱导信号级联反应，最终导致促炎介质如细胞因子、趋化因子和共刺激分子的产生。本综述重点关注鞭毛蛋白的作用机制及其对先天免疫和适应性免疫的影响。
