哺乳动物Toll样受体对结核分枝杆菌的控制

针对胞内菌结核分枝杆菌最为有效的免疫应答主要取决于天然免疫应答对侵入细菌的早期发现及获得性免疫应答的活化。Toll样受体在天然免疫应答发现分枝杆菌相关性分子和介导抗菌效应分子的分泌上起作用。它能调节一些免疫调节分子,这些分子能促进基于Th1细胞的T细胞发育。因此,Toll样受体的活化在抗微生物感染的机制上起一定的作用。     

Toll样受体介导的脂磷壁酸生物学效应

Toll样受体是新近发现的一组介导天然免疫的受体。Toll样受体在革兰阳性茵脂磷壁酸的各生物学效应中发挥了启动作用,Toll样受体的信号通路是最终产生天然免疫的途径,在脂磷壁酸抗感染免疫中Toll样受体2、Toll样受体4起了关键作用。脂磷壁酸在抗肿瘤免疫等其他生物学效应中的作用还有待进一步证实。另外介绍了一些受体相关分子MyD88、MD-2、CDl4,它们在Toll样受体介导的脂磷壁酸各生物学效应的信号传导中起了重要作用。     

天然免疫进化中的无脊椎动物Toll样受体

Toll样受体（Toll-like receptors,TLR）（或Toll）通过与各种病原相关分子模式（pathogen associated molecular patterns,PAMP）的识别和特异结合,广泛参与各种天然免疫应答,目前已在线虫类、软体动物、节肢动物、棘皮动物及低等脊索类的后口动物等多种无脊椎动物中发现大量的TLR及同源蛋白.TLR在进化中高度保守,其功能随着动物进化中免疫机能的复杂化而多样化.这些研究成果将会不断加深对无脊椎动物天然免疫系统的起源、进化路线及其信号转导机制的认识.     

Toll样受体的研究进展

Toll样受体是近几年发现的天然免疫受体,它们不仅能特异性地识别病原微生物的结构成分,激活天然免疫,同时也为激活获得性免疫提供共刺激信号。Toll样受体是天然免疫与获得性免疫之间的连接点。     

Toll 样受体与天然免疫

Toll样受体家族是一类模式识别受体,它介导了一个植物,昆虫,哺乳动物共同拥有的高度保守的信号通路。最近几年相继发现了多种人类Toll样受体以及相关的病原微生物配体,这些配体涵盖了病毒,细菌,真菌等微生物上多种保守的病原相关分子模式。可见Toll样受体在多种病原微生物及其产物的识别和免疫防御反应中有重要的作用。     

Toll样受体识别机制及其生物学意义

Toll样受体介导的信号转导通路在对抗外来病原体的天然免疫应答中起重要作用。Toll样受体是一个天然模板识别受体家族,能识别固有性模板(微生物和哺乳动物所共有的病原相联的分子模板PAMPs)。Toll样受体通过巨噬细胞和其他免疫细胞来识别,其中TLR4识别内毒素、TLR2识别肽聚糖、TLR9识别细菌DNA、TLR5识别鞭毛蛋白、TLR3识别双链RNA等。本探讨了多种Toll受体家族成员在动物体内识别机理及功能,概述了其应用研究进展。     

靶向 Toll 样受体的免疫调节剂研究进展

Toll 样受体是一类相对保守的模式识别受体,可以识别损伤相关分子模式和病原相关分子模式,从而启动天然免疫应答,在天然免 疫过程中发挥非常重要的作用。其介导的信号通路失调会引发各种炎症反应、癌症和自身免疫病等疾病。综述近年与 Toll 样受体有关的免 疫调节剂的研究进展,并概括与之相关的疾病,为靶向 Toll 样受体的免疫调节剂的研发提供一定参考。     

Toll样受体(TLRs)的信号转导与免疫调节

Toll样受体(Toll-like receptors,TLRs)是进化中比较保守的一个受体家族,至少包括10个成员.TLRs能特异地识别病原相关的分子模式(PAMPs),不仅在激活天然免疫中发挥重要的作用,而且还调节获得性免疫,是连接天然免疫和获得性免疫的桥梁.近年来,TLRs信号转导的研究,特别是在负调控研究领域,进展非常迅速.对TLRs信号通路新进展以及TLRs在抗感染免疫中的作用进行了综述.     

Toll样受体与树突状细胞介导的天然免疫和获得性免疫

树突状细胞(dendritic cells,DCs)作为迄今所发现的抗原提呈功能最强的一类抗原提呈细胞,是联结天然免疫和获得性免疫的桥梁。Toll样受体(Toll-like receptors,TLRs)是一类进化保守的胚系编码的模式识别受体,在DCs的抗原识别、递呈及激活T细胞等方面具有重要作用,是机体受外来抗原入侵后作出适当免疫反应的调控点。现就TLRs在不同DCs亚群中的分布、与DCs介导的天然免疫和获得性免疫的关系及DCs功能可塑性的分子基础作一综述。     

固有免疫应答与动脉粥样硬化关系的研究进展

固有免疫应答在动脉粥样硬化(atherosclerosis,As)的发生和发展中起重要作用．固有免疫应答细胞,包括单核/巨噬细胞、肥大细胞、自然杀伤细胞、中性粒细胞和树突状细胞,是机体抵御微生物和异物入侵的第一道防线．这些细胞广泛参与As中泡沫细胞形成、斑块内基质降解、细胞凋亡、血管新生和斑块破裂等事件．模式识别受体是免疫细胞上识别病原体(或某些内源性成分)相关分子模式的一类受体分子,包括Toll样受体和NOD样受体,介导固有免疫应答反应．Toll样受体在固有免疫应答细胞中具有不同程度的表达,在As中具有不同的作用,如TLR2和TLR4对As起促进作用,而TLR3具有As保护作用．NLRP3炎性体与动脉血管壁的早期损伤有关．对固有免疫应答细胞及模式识别受体在As形成中的作用进行深入研究,不仅有助于理解As的形成过程,而且还能为临床上防治心血管类疾病提供了新的治疗靶点和诊断指标．     

Toll样受体信号传导途径的研究进展

Toll样受体家族（Toll-like receptors,TLRs）成员在固有免疫反应,尤其是调节吞噬细胞（如巨噬细胞等）特异性识别微生物病原体抗原,分泌促炎细胞因子,上调共刺激分子,并诱导机体适应性免疫反应抗微生物病原体感染中发挥重要调控作用,被称为机体固有免疫和适应性免疫调节中的辅助受体（adjuvant receptor）。目前,对Toll样受体家族成员调控免疫反应信号传导途径的研究已成为分子免疫学领域的研究热点,认为主要存在髓样分化蛋白88（MyD88,是一种转接蛋白）依赖性和MyrD88非依赖性两条主要调控途径。本文仅就Toll样受体信号传导途径的研究进展作以简要综述。     

Toll-like receptors and innate immunity

Toll-like receptors (TLRs) are evolutionarily conserved innate receptors expressed in various immune and non-immune cells of the mammalian host. TLRs play a crucial role in defending against pathogenic microbial infection through the induction of inflammatory cytokines and type I interferons. Furthermore, TLRs also play roles in shaping pathogen-specific humoral and cellular adaptive immune responses. In this review, we describe the recent advances in pathogen recognition by TLRs and TLR signaling.     

Microbial patterns signaling via Toll-like receptors 2 and 5 contribute to epithelial repair, growth and survival

Epithelial cells (ECs) continuously interact with microorganisms and detect their presence via different pattern-recognition receptors (PRRs) including Toll-like receptors (TLRs). Ligation of epithelial TLRs by pathogens is usually associated with the induction of pro-inflammatory mediators and antimicrobial factors. In this study, using human airway ECs as a model, we found that detection of microbial patterns via epithelial TLRs directly regulates tissue homeostasis. Staphylococcus aureus (S. aureus) and microbial patterns signaling via TLR2 and TLR5 induce a set of non-immune epithelial responses including cell migration, wound repair, proliferation, and survival of primary and cancerous ECs. Using small interfering RNA (siRNA) gene targeting, receptor-tyrosine kinase microarray and inhibition studies, we determined that TLR and the epidermal growth factor receptor (EGFR) mediate the stimulating effect of microbial patterns on epithelial repair. Microbial patterns signaling via Toll-like receptors 2 and 5 contribute to epithelial repair, growth and survival. This effect is independent of hematopoietic and other cells as well as inflammatory cytokines suggesting that epithelia are able to regulate their integrity in an autonomous non-inflammatory manner by sensing microbes directly via TLRs.     

Toll-like receptors: a family of pattern-recognition receptors in mammals

The innate immune system uses a variety of germline-encoded pattern-recognition receptors that recognize conserved microbial structures or pathogen-associated molecular patterns, such as those that occur in the bacterial cell-wall components peptidoglycan and lipopolysaccharide. Recent studies have highlighted the importance of Toll-like receptors (TLRs) as a family of pattern-recognition receptors in mammals that can discriminate between chemically diverse classes of microbial products. First identified on the basis of sequence similarity with the Drosophila protein Toll, TLRs are members of an ancient superfamily of proteins, which includes related proteins in invertebrates and plants. TLRs activate innate immune defense reactions, such as the release of inflammatory cytokines, but increasing evidence supports an additional critical role for TLRs in orchestrating the development of adaptive immune responses. The sequence similarity between the intracellular domains of the TLRs and the mammalian interleukin-1 and interleukin-18 cytokine receptors reflects the use of a common intracellular signal-transduction cascade triggered by these receptor classes. But more recent findings have demonstrated that there are in fact TLR-specific signaling pathways and cellular responses. Thus, TLRs function as sentinels of the mammalian immune system that can discriminate between diverse pathogen-associated molecular patterns and then elicit pathogen-specific cellular immune responses.     

Toll-like receptors: mammalian "taste receptors" for a smorgasbord of microbial invaders

In Drosophila, the Toll family of proteins is responsible for the recognition of bacteria and fungi. In mammals, Toll-like receptors (TLRs) are able to recognize and respond to microbial pathogens. Recent findings have defined the relationship between many TLRs and their microbial ligands, as well as the effect of TLR ligation on host defense. These findings have also provided a framework for determining how TLRs may by used to therapeutically modulate immune responses to infection.     

Toll-like receptors: linking innate and adaptive immunity

Detection of and response to microbial infections by the immune system depends largely on a family of pattern-recognition receptors called Toll-like receptors (TLRs). These receptors recognize conserved molecular products derived from various classes of pathogens, including Gram-positive and -negative bacteria, DNA and RNA viruses, fungi and protozoa. Recognition of ligands by TLRs leads to a series of signaling events resulting in induction of acute responses necessary to kill the pathogen. TLRs are also responsible for the induction of dendritic cell maturation, which is responsible and necessary for initiation of adaptive immune responses. Although TLRs control induction of adaptive immunity, it is not clear at this point how responses are appropriately tailored by individual TLRs to the advantage of the host.     

Role of toll-like receptors in tissue repair and tumorigenesis

Toll-like receptors (TLRs) play a critical role in host defense from microbial infection. TLRs recognize conserved molecular structures produced by microorganisms and induce activation of innate and adaptive immune responses. The inflammatory responses induced by TLRs play an important role TLRs not only in host defense from infection, but also in tissue repair and regeneration. This latter function of TLRs can also contribute to tumorigenesis. Here we review recent progress in understanding the role of TLRs in cancer development.     

人Toll样受体靶向药物研究进展

Toll样受体(TLR)是一类模式识别受体,通过多种信号传递改善免疫系统功能,活化NF-κB信号通路,调节TNF-α、ILs和IFN-α等多种细胞因子分泌,在天然免疫系统中发挥重要作用,在免疫学及药物研究领域受到广泛关注。TLR种类众多,配体广泛,可以作为治疗微生物感染、炎症、自身免疫性疾病、 肿瘤及放射损伤等疾病的药物靶点,是免疫治疗的重要切入点。研究人员已经对数十种TLR靶向药物进行了研究。对TLR结构特征、信号传递以及靶向药物的特点和研究现状进行综述,分析其在免疫治疗方面的优劣势,也为下一步药物研究提供一定的理论依据。     

Microbe‐inducible trafficking pathways that control Toll‐like receptor signaling

The receptors of the mammalian innate immune system are designed for rapid microbial detection, and are located in organelles that are conducive to serve these needs. However, emerging evidence indicates that the sites of microbial detection are not the sites of innate immune signal transduction. Rather, microbial detection triggers the movement of receptors to regions of the cell where factors called sorting adaptors detect active receptors and promote downstream inflammatory responses. These findings highlight the critical role that membrane trafficking pathways play in the initiation of innate immunity to infection. In this review, we describe pathways that promote the microbe‐inducible endocytosis of Toll‐like receptors (TLRs), and the microbe‐inducible movement of TLRs between intracellular compartments. We highlight a new class of proteins called Transporters Associated with the eXecution of Inflammation (TAXI), which have the unique ability to transport TLRs and their microbial ligands to signaling‐competent regions of the cell, and we discuss the means by which the subcellular sites of signal transduction are defined.      

Toll-like receptors: lessons from knockout mice

The Toll signalling pathway, which is required for establishment of dorsoventral polarity in Drosophila embryos, plays an important role in the response to microbial infections. Recently, Toll-like receptors (TLRs) have also been identified in mammals. TLR4 has been shown to function as the transmembrane component of the lipopolysaccharide receptor, while TLR2 recognizes peptidoglycans from Gram-positive bacteria, lipoproteins and yeast. Although various microbial cell-wall components are recognized by different receptors, all of these responses are abrogated in MyD88-deficient cells. These results show that different TLRs recognize different microbial cell-wall components, and that MyD88 is an essential signalling molecule shared among interleukin-1 receptor/Toll family members.