TLRs介导的RNA病毒识别及固有免疫应答.doc

TLRs介导的RNA病毒识别及固有免疫应答 [摘要] 固有免疫（innate immunity）又称非特异性免疫 ( nonspecific immunity)，是人体抵抗外来生物入侵的第一道防线。与适应性免疫相比，固有免疫具有作用范围广、反应出现快、参与反应的免疫细胞多、相对稳定性和遗传性等特点。近年来，固有免疫在分子水平上的识别及调控机制越来越受到关注。哺乳动物的固有免疫识别及调控主要通过一系列的模式识别受体( pattern recognition receptor，PRR)识别病原微生物上表达的保守的病原体相关分子模式( pathogen associated molecular pattern，PAMP) 来实现，这种形式让机体不但可以发现入侵的病原体，而且能够识别其类型，并通过一系列信号途径活化效应分子，识别自我与非我，激活与调控固有免疫应答，并且相互协同或互相调节以形成调控网络，从而控制并清除病原体，在固有免疫中发挥独特的功能。本文主要介绍TLRs介导的宿主细胞对RNA病毒感染的识别以及固有免疫应答。 [关键字] 固有免疫；模式识别受体；RNA病毒；TLRs [Abstract] Innate immunity, also known as nonspecific immunity, is the first defense against the pathogen invasion. Compared with adaptive immunity, there are lots of characteristics of innate immunity such as the wide range of effects, rapid reaction, more immune cells involved in the reaction. In recent years, the molecular mechanism of the recognition and regulation in innate immunity has received more and more attention. The innate immune recognition and regulation of mammalian species is achieved by a series of pattern recognition receptors (PRRs) that recognize the pathogen associated molecular pattern (PAMPs) expressed on pathogenic microorganisms, which can not only help the body find the invasion of pathogens, but also identify its type. In this way the body can identify self and non-self and activate the innate immune response, removing pathogens. In this paper, we pay mainly attention on the recognition of host cells for RNA virus infection mediated by TLRs and the innate immune response induced . [Key words] innate immune; PAMPs; PRRs; RNA virus; TLRs; RLRs; NLRs PRRs对PAMP的识别可以明显上调参与炎症反应的基因的转录。这些基因主要编码炎性细胞因子（趋化因子）、I型干扰素（IFNI）、和抗菌蛋白等。I型干扰素（IFN-α和IFN-β）的产生在抗病毒应答反应中起着关键作用，它可以诱导影响蛋白质合成，生长调节以及细胞凋亡的基因的表达，同时可以加快树突状细胞的成熟、增强自然杀伤细胞的细胞毒性以及促进病毒特异性的T淋巴细胞分化成熟，从而引发机体适应性免疫应答。[1] 宿主PRRs可以识别的病毒PAMPs包括基因组DNA、单链RNA（ss-RNA）、双链RNA（dsRNA）、５’－末端三磷酸化的RNA和病毒蛋白。与RNA病毒感染识别有关的PRRs有三类：Toll样受体（Toll-like receptors, TLRs）、维甲酸诱导基因Ｉ样受体（Retinoic acid-inducible gene Ｉ（RIG-Ｉ）-like receptors