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[固有免疫:Toll样受体的结构与功能]

[Innate immunity: structure and function of TLRs].

作者信息

Delneste Yves, Beauvillain Céline, Jeannin Pascale

机构信息

Inserm U564, Equipe Avenir, Université d'Angers, 4, rue Larrey, 49933 Angers Cedex 9, France.

出版信息

Med Sci (Paris). 2007 Jan;23(1):67-73. doi: 10.1051/medsci/200723167.

Abstract

The innate immune system provides the first line of defence against infection. Through a limited number of germline-encoded receptors called pattern recognition receptors (PRRs), innate cells recognize and are activated by highly conserved structures expressed by large group of microorganisms called pathogen-associated molecular patterns (PAMPs). PRRs are involved either in recognition (scavenger receptors, C-type lectins) or in cell activation (Toll-like receptors or TLR, helicases and NOD molecules). TLRs play a pivotal role in cell activation in response to PAMPs. TLR are type I transmembrane proteins characterized by an intracellular Toll/IL 1 receptor homology domain that are expressed by innate immune cells (dendritic cells, macrophages, NK cells), cells of the adaptive immunity (T and B lymphocytes) and non immune cells (epithelial and endothelial cells, fibroblasts). In all the cell types analyzed, TLR agonists, alone or in combination with costimulatory molecules, induce cell activation. The crucial role played by TLR in immune cell activation has been detailed in dendritic cells. A TLR-dependent activation of dendritic cells is required to induce their maturation and migration to regional lymph nodes and to activate naïve T cells. The ability of different cell types to respond to TLR agonists is related to the pattern of expression of the TLRs and its regulation as well as their intracellular localization. Recent studies suggest that the nature of the endocytic and signaling receptors engaged by PAMPs may determine the nature of the immune response generated against the microbial molecules, highlighting the role of TLRs as molecular interfaces between innate and adaptive immunity. In this review are summarized the main biological properties of the TLR molecules.

摘要

先天性免疫系统提供了抵御感染的第一道防线。通过有限数量的种系编码受体,即模式识别受体(PRR),先天性细胞识别并被一大类微生物表达的高度保守结构激活,这些结构称为病原体相关分子模式(PAMP)。PRR参与识别(清道夫受体、C型凝集素)或细胞激活(Toll样受体或TLR、解旋酶和NOD分子)。TLR在响应PAMP的细胞激活中起关键作用。TLR是I型跨膜蛋白,其特征是具有细胞内Toll/IL-1受体同源结构域,由先天性免疫细胞(树突状细胞、巨噬细胞、NK细胞)、适应性免疫细胞(T和B淋巴细胞)和非免疫细胞(上皮和内皮细胞、成纤维细胞)表达。在所有分析的细胞类型中,TLR激动剂单独或与共刺激分子联合使用均可诱导细胞激活。TLR在免疫细胞激活中所起的关键作用已在树突状细胞中详细阐述。树突状细胞的TLR依赖性激活是诱导其成熟并迁移至局部淋巴结以及激活初始T细胞所必需的。不同细胞类型对TLR激动剂的反应能力与其TLR的表达模式及其调节以及细胞内定位有关。最近的研究表明,PAMP所涉及的内吞和信号受体的性质可能决定针对微生物分子产生的免疫反应的性质,突出了TLR作为先天性免疫和适应性免疫之间分子界面的作用。本文综述了TLR分子的主要生物学特性。

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