Toll样受体与免疫排斥

随着Toll样受体(TLR)的发现,固有免疫应答如何调控适应性免疫应答已成为研究的热点。许多研究结果表明,微生物分子触发的病原体相关分子模式(PAMP)和TLR可以被内源性配体激活,并在哺乳动物体内表达。这些“危险信号”在器官移植后对于缺血再灌注损伤的发生、移植器官功能的影响及存活时间都起着重要的作用。     

Toll样受体介导的抗病毒天然免疫

病毒能否在细胞内生存和复制取决于宿主的抗病毒机制.天然免疫(Innate immunity)作为机体抗感染免疫的第一道防线,主要在获得性免疫(Adaptive immunity)活化前,发挥抗感染作用.     

人类Toll样受体信号转导途径及其介导的免疫作用

人类Toll样受体（TLR）是近年来发现的一类新的细胞表面信号传导跨膜受体,是人体固有免疫和适应性免疫的桥梁。TLR4组织分布较广泛,激活后通过TLR4-NF-κB信号途径促进细胞因子合成、激活T细胞、调节Th1／Th2免疫反应的平衡,从而调节机体的免疫状态。进一步研究TLR4的信号转导途径及其在疾病发展过程中的表达情况,可以为临床预防和治疗疾病提供新的思路和方法。     

Toll样受体在机体抗病毒免疫反应中的作用

哺乳动物的Toll样受体(TLR)家族具有模式识别受体的功能,其可以识别微生物的保守分子成分,启动机体的固有免疫系统,从而帮助机体清除病原体.利用TLR敲除的动物或细胞模型进行的研究使人们认识到TLR在机体抗病毒免疫反应中发挥着重要作用.病毒与宿主细胞的TLR结合后,通过NF-κB或IRF-3的信号路径激活细胞因子的表达,从而激发免疫应答.研究TLR如何与病原体结合及如何激活下游基因对深入认识病原体所致相关疾病的发病机制、免疫应答及病理生理具有重要的意义,并为病毒性疾病的临床治疗或免疫预防提供新的思路.     

Toll样受体介导抗HBV感染免疫

Toll样受体(TLRs)的发现,使人们对HBV感染免疫有了新的认识.目前研究认为,TLRs除了介导抗HBV感染天然免疫外,还能促进树突状细胞(DC)成熟,调节Th1/Th2型免疫,参与抗HBV特异性免疫,同时,HBV也影响某些TLRs的表达,这可能是HBV感染慢性化的原因之一.进一步明确TLRs在HBV感染免疫中的作用,可为HBV感染的治疗提供一个新的切入点.     

Toll样受体介导的固有免疫应答在HBV感染中的研究进展北大核心CSCD

乙型肝炎病毒（hepatitis B virus,HBV）感染仍是全球重大公共卫生问题,HBV入侵机体后产生持续性感染涉及的免疫机制十分复杂,HBV在与宿主免疫系统的博弈中也进化出了一系列策略影响固有免疫效应,异常的固有免疫可能是导致病毒持续性感染的诱因之一.病原体相关分子模式（pathogen associated molecular patterns,PAMPs）被模式识别受体（pathogens recognition recep-tors,PRRs）识别进而启动固有免疫应答.Toll样受体（Toll like receptors,TLRs）是PRRs家族的重要成员,TLRs介导的固有免疫应答在与HBV相互作用并引起HBV感染相关的免疫效应中发挥重要作用,关系到病毒的早期清除和随后特异性免疫应答的激活.本文就TLRs介导的固有免疫应答与HBV之间相互作用的研究进展以及基于TLRs免疫治疗策略的相关成果进行综述.     

Toll样受体与肿瘤免疫

肿瘤作为临床的常见病，其形成的主要原因之一是肿瘤细胞具有逃避宿主免疫系统识别及清除的能力。这种免疫逃逸机制包括：下调对抗原处理的能力及提呈的成分、产生抑制免疫应答的细胞因子以及诱导肿瘤抗原特异性T细胞耐受等。近年来随着天然免疫研究的不断发展，人们逐渐关注天然免疫与机体抗肿瘤的关系。Toll样受体家族（Toll like receptors，TLRs）成员属模式识别受体（Pattem recognition receptor，PRR），是重要的天然免疫分子。目前对其研究主要集中在对细菌及病毒的识别机制上，并被视为联系天然免疫与获得性免疫之间的桥梁。但是近来发现，部分TLRs基因序列的多态性与前列腺癌的发生存在相关性；TLRs介导的信号通路能够活化树突状细胞，继而直接增强宿主对肿瘤天然免疫及获得性免疫应答的能力。而某些肿瘤细胞表面表达的TLRs则与肿瘤的免疫逃逸有关。     

Toll样受体介导的先天性抗病毒免疫反应研究进展

TLRs是先天性免疫系统最重要的模式识别受体,通过识别病毒的PAMPs/DAMPs,活化依赖和非依赖于MyD88的信号通路,诱导I-IFN、炎性因子和趋化因子等的释放,发挥抗病毒作用.现就TLRs的基本概况、结构特征、抗病毒信号通路及对不同病毒的天然免疫反应等相关研究进展进行简要综述.     

抗病毒感染的固有免疫机制

病毒感染性疾病仍然是一个具有挑战性的全球健康问题.在人类传染病中,病毒感染性疾病高达60%～65%.虽然人类多年来的研究成果为预防、控制和治疗各类病毒感染性疾病做出了巨大的贡献,但是人类与病毒之间的战斗未有穷期,甚至有些已受控制的病毒感染性疾病可能卷土重来.已知机体抗病毒感染不仅依赖病毒特异性抗体的中和作用,更依赖于...     

Toll样受体与变态反应关系研究进展

在研究天然免疫应答对适应性免疫应答的影响过程中，Toll样受体(Toli-like receptors，TLRs)的发现引起了人们极大的兴趣。近来研究表明TLRs途径可能介导了树突状细胞、T淋巴细胞和肥大细胞之间的相互作用，从而调节变态反应。通过树突状细胞不同亚群的鉴定和T调节细胞以及肥大细胞上TLRs的发现，调控TLRs可能会开辟治疗变态反应性疾病的新纪元。     

Reading the viral signature by Toll-like receptors and other pattern recognition receptors

Successful host defense against viral infections relies on early production of type I interferon (IFN) and subsequent activation of a cellular cytotoxic response. The acute IFN and inflammatory response against virus infections is mediated by cellular pattern-recognition receptors (PRRs) that recognize specific molecular structures on viral particles or products of viral replication. Toll-like receptors (TLRs) constitute a class of membrane-bound PRRs capable of detecting microbial infections. While TLR2 and TLR4, which were first identified to recognize Gram-positive and Gram-negative bacteria, respectively, sense specific viral proteins on the cell surface, TLRs 3, 7, 8, and 9 serve as receptors for viral nucleic acids in endosomic compartments. In addition to TLRs, cells express cytoplasmic PRRs such as the RNA helicase retinoic acid inducible gene I and the kinase double-stranded RNA-activated protein kinase R, both of which sense dsRNA, a characteristic signature of viral replication, and initiate a protective cellular response. Here we review the recent progress in our understanding of PRRs and viral infections and discuss the molecular and cellular responses evoked by virus-activated PRRs. Finally, we look into what is currently known about the role of PRRs in viral infections in vivo.     

Toll-like receptors on the fork roads between innate and adaptive immunity

There is a permanent interaction amid the innate and adaptive immune systems that leads to a defensive immune response against pathogens and contributes substantially to self-nonself discrimination. Toll-like receptors (TLRs) are essential molecules of the innate immune system that stimulate numerous inflammatory pathways and harmonize systemic defense against a wide array of pathogens. In addition to identifying unique molecular patterns associated with various sections of pathogens, TLRs may also recognize a number of self proteins and endogenous nucleic acids. Several reports have indicated that inappropriate stimulation of the TLR pathway via endogenous or exogenous ligands in animal models or humans may lead to the induction and/or prolongation of autoimmune response and tissue injury.     

先天免疫Toll样受体在哮喘病中作用的研究进展

哮喘病的高发性和普遍性使哮喘病成为人们极度关注的健康问题,哮喘病的特征是呼吸道阻塞和支气管的过度炎性反应.虽然对后大获得性免疫在哮喘病中的作用已进行了广泛地研究,但是先天免疫在哮喘病中的重要件是最近才被发现的.先大免疫不但提供抗感染的第一道防线,而且调控后天获得件免疫的激活.Toll样受体是先大免疫的关键感受器,它也是研究最多的模式识别受体.激活的Toll样受体信号传导通路可以很快引起与炎性反应和免疫反应相关的各种基因的表达.本义综述了了目前天于Toll样受体在哮喘病中作用的研究进展.     

Translational mini-review series on Toll-like receptors: networks regulated by Toll-like receptors mediate innate and adaptive immunity

The Toll-like receptor (TLR) family provide key components of mammalian immunity and are part of the earliest surveillance mechanisms responding to infection. Their activation triggers the innate immune response, and is crucial to the successful induction of Th1/Th2-phenotyped adaptive immunity. Innate immunity was long considered to be non-specific and somewhat simple compared to adaptive immunity, mediated via the engulfment and lysis of microbial pathogens by phagocytic cells such as macrophages and neutrophils, and involving no complex protein-protein interactions. The emergence of the TLR field has contributed to a revision of our understanding, and innate immunity is now viewed as a highly complex process, in line with adaptive immunity. This review will give a brief overview of our current knowledge of TLR biology, and will focus on TLRs as key components in complex networks that activate, integrate and select the appropriate innate and adaptive immune responses in the face of immunological danger.     

Toll-like receptors' two-edged sword: when immunity meets apoptosis

Toll-like receptors (TLR) have emerged as key players in the detection of pathogens and the induction of anti-microbial immune response. TLR recognize pathogen-associated molecular patterns, and trigger anti-microbial innate immune responses ranging from the secretion of pro-inflammatory mediators to the increase of natural killer cell cytotoxicity. Besides activating the innate immune response, TLR engagement also shapes the adaptive immune response. Indeed, the broad diversity of signaling pathways initiated by TLR is progressively unraveled. Recent reports suggested that among the anti-microbial defenses they initiate, members of the TLR family can induce apoptosis. This review focuses on this newly described function of TLR, and emphasizes the similarities and differences between the different apoptosis-signaling pathways described downstream of TLR. The functional relevance of TLR-triggered apoptosis is also discussed, as therapeutic applications are likely to ensue in the near future.     

Toll样受体与急性胰腺炎

急性胰腺炎（AP）是一个临床常见的疾病,在大多数病人是一个良性自限的病程,称为水肿性胰腺炎。而如果病情恶化,伴发胰腺的坏死,炎症细胞因子的活化,从而导致多器官功能衰竭,则称为坏死性胰腺炎。迄今为止,其详细的发病机理是不清楚的。作为固有免疫重要部分的Toll样受体（TLR）在胰腺炎过程中起重要的作用,但也有人提出异议。     

Syk kinase is required for collaborative cytokine production induced through Dectin-1 and Toll-like receptors

Recognition of microbial components by germ-line encoded pattern recognition receptors (PRR) initiates immune responses to infectious agents. We and others have proposed that pairs or sets of PRR mediate host immunity. One such pair comprises the fungal beta-glucan receptor, Dectin-1, which collaborates through an undefined mechanism with Toll-like receptor 2 (TLR2) to induce optimal cytokine responses in macrophages. We show here that Dectin-1 signaling through the spleen tyrosine kinase (Syk) pathway is required for this collaboration, which can also occur with TLR4, 5, 7 and 9. Deficiency of either Syk or the TLR adaptor MyD88 abolished collaborative responses, which include TNF, MIP-1alpha and MIP-2 production, and which are comparable to the previously described synergy between TLR2 and TLR4. Collaboration of the Syk and TLR/MyD88 pathways results in sustained degradation of the inhibitor of kappaB (IkappaB), enhancing NFkappaB nuclear translocation. These findings establish the first example of Syk- and MyD88-coupled PRR collaboration, further supporting the concept that paired receptors collaborate to control infectious agents.     

Toll样受体2、4对病毒囊膜蛋白的识别

TLR2、4是TLRs家族中重要的成员,通过识别囊膜病毒的PAMPs/DAMPs,活化依赖和非依赖于MyD88的信号通路,诱导促炎性细胞因子和趋化因子等的释放,介导先天性抗病毒免疫反应。本文就TLR2、4的基本概况、结构特征、抗病毒信号通路以及对不同囊膜病毒的天然免疫反应等相关研究进展进行简要综述。     

Mechanisms of innate immune responses mediated by Toll-like receptors

The innate immune response is thought to be a rapid and nonclonal host defense. The recent discovery of Toll-like receptors (TLRs) and analyses of their physiological roles have established the notion that TLRs play a central role in innate immunity. Accumulating evidence suggests that individual TLRs recognize distinct ligands derived from bacterial components to generate specific cellular immune responses. In this review, we delineate the relationships between TLRs and microbial components, the TLR-mediated signaling pathways mainly based on cytoplasmic adaptor molecules containing Toll/interleukin-1R domains, the mechanism of TLR-mediated gene expression, and the involvement of TLRs in septic shock, including up-to-date observations.