树突状细胞TLR7/8信号通路机制的研究进展

树突状细胞(dendritic cells,DCs)是抗原提呈功能最强的细胞,也是联接天然免疫和获得性免疫的桥梁和纽带。Toll样受体(Toll-like receptors,TLRs)是天然免疫中重要的模式识别受体(pattern recognition receptor,PRR),在DCs分化和功能成熟中发挥重要作用。它能够识别细菌、真菌、病毒、原虫等病原体的高度保守结构基序——病原体相关分子模式(pathogen-associated molecular patterns,PAMPs),在机体抗病原体感染中发挥重要作用。人浆细胞样DCs(plasmacytoid     

Toll样受体在丙型肝炎慢性化中的作用机制

世界上约有3%的人感染了丙型肝炎病毒(HCV),其中55%～85%的感染者发展成为慢性感染[1].不同的个体感染后的自然病程和结局存在较大差异.Toll样受体(TLRs)能够识别病毒的单链RNA,在病毒感染中参与病原体的识别和宿主反应.本文就TLRs在慢性丙型肝炎(CHC)发病机制中的研究进行综述.     

MicroRNA、Toll样受体与HIV发病机制慢性免疫激活的研究进展

获得性免疫缺陷综合征(AIDS)是由人类免疫缺陷病毒(HIV)感染所致的致命性疾病。该病毒侵犯并摧毁宿主的免疫系统,初始感染CD4~+T细胞,逐渐呈现出慢性免疫激活的状态并最终导致AIDS的发生。MicroRNAs(miRNA),小型非编码RNA,在控制HIV病毒的感染及复制过程中发挥着重要的作用。Toll样受体(TLRs)在病原体诱导的免疫激活现象中起决定性的作用。本综述阐述了miRNA与HIV病毒间的相关联系,并介绍miRNA在AIDS发病机制慢性免疫激活的作用及其与TLRs的关系。     

Toll受体9对配体的识别及信号传导的研究进展

Toll样受体(Toll-like receptors,TLRs)是一类重要的模式识别受体,在识别病原微生物方面具有重要作用。到目前为止,TLRs在哺乳动物的身上共发现了13种,即TLR1～TLR13[1],其中TLR9识别的配体主要是细菌和病毒的DNA。本文现就近     

Toll样受体与疾病

天然免疫反应是机体抵御外界微生物感染的第一道防线。固有免疫系统通过模式识别受体(PRRs)识别病原微生物的病原相关分子模式(PAMPs)。PAMPs在结构上相对保守,主要存在于微生物。Toll样受体家族是最重要的PRRs,通过识别相应的PAMPs介导天然免疫反应,同时通过DCs启动适应性免疫应答。另外,TLRs能够识别某些内源性的TLR配体,这些配体称之为损伤相关分子模式(DAMPs)。研究发现TLRs在抗感染、变态反应、自身免疫性疾病、肿瘤等疾病的发生发展过程中起着重要的作用。在深入研究Toll样受体及其信号通路的基础上,以其作为药物干预靶点,对治疗相关感染性疾病、自身免疫性疾病、变态反应性疾病等具有重要的科学意义和应用价值。     

Toll样受体功能研究进展

表达在免疫细胞上的Toll样受体(TLRs)通过识别已知的病原体相关的分子模式(PAMPs)在宿主防御入侵的病原体过程中起着决定性的作用,是针对病原体和肿瘤细胞的固有免疫应答的感受器.Toll样受体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.Toll样受体也表达在非免疫细胞上,如内皮细胞和上皮细胞等.细菌感染可能通过Toll样受体影响这些细胞的功能,从而导致局部感染或炎症进程并因此来促进肿瘤发生;而且表达在肿瘤细胞上的Toll样受体被认为可以通过TLRs信号传导引起肿瘤细胞增殖、转移和抵抗细胞凋亡.     

Toll样受体信号通路在眼缺血综合征中的作用与研究

眼缺血综合征（OIS）是由于颈动脉阻塞或狭窄所致的脑和眼的供血不足而产生的一系列脑和眼的症状,其发病机制尚不十分清楚。Toll样受体（TLRs）是机体免疫系统识别、感知细菌、病毒等病原体入侵的重要分子,在机体免疫防御功能中发挥着重要作用。众多的研究提示,OIS的发生发展与视网膜长期缺血缺氧导致的慢性炎症有关,其中Tou样受体起着重要的作用。文章以TLRs介导的信号通路为切入点,探讨免疫系统的激活与OIS发病过程的相互关系。为其病理机制及防治OIS提供新的思路和方法。     

Toll 样受体与系统性红斑狼疮关系的研究进展

系统性红斑狼疮(SLE)是一种复杂的以出现多种自身抗体为特征的自身免疫性疾病,可以累及多个系统。有多种因素参与了SLE的发病机制,其中免疫因素在SLE的发病机制中尤为突出。Toll样受体(TLRs)作为一种重要的模式识别受体,能够识别病原微生物的结构组分和代谢产物,构成机体免疫第一道防线。TLRs信号转导对固有免疫及获得性免疫均具有重要的调节作用。近年研究发现TLRs在SLE的发病机理中起重要作用,本文就此作一综述。     

Toll样受体及其与恶性血液病关系的研究进展

Toll样受体(Toll-like receptors,TLRs)是一类天然免疫的模式识别受体.机体通过TLRs识别并结合相应病原相关分子模式,启动激活信号转导途径,并诱导某些免疫效应分子表达,激活天然免疫、参与和调节获得性免疫应答.近年来TLRs在非实体瘤中作用的研究逐渐增多,已有研究表明它有可能成为恶性血液病免疫治疗的靶点.该文就TLRs与恶性血液病关系的研究进展作一综述.     

Toll样受体及其与眼部炎性疾病的关系

Toll样受体(Toll-like receptors,TLRs)是一类广泛存在于哺乳动物细胞的跨膜受体,它可以识别许多病原微生物保守的病原相关分子模式(pathogen associated molecular patterns,PAMPs),参与细胞信号传导及免疫反应,在抗感染中发挥重要作用.该文就Toll样受体家族成员的结构特点、其信号传导通路及宿主免疫的功能、及其与眼部炎性疾病的联系进行综述.为深入研究眼部感染性及免疫性疾病的发病机制提供帮助,为这些疾病的治疗提供新的思路和手段.     

The role of Toll-like receptors in immune disorders

Toll-like receptors (TLRs) play an important role in innate immunity. Individual TLRs recognise microbial components that are conserved among pathogens. Such recognition initiates necessary inflammatory immune responses and induces subsequent activation of adaptive immunity. Studies in people with polymorphisms in genes encoding TLR signalling can elucidate the relationship between TLRs and human diseases, such as infectious diseases, atherosclerosis and immunodeficiency. Indeed, accumulating data in respect to TLR signalling suggest that TLRs are closely related with the pathogenesis of autoimmune diseases. This review looks at the role of TLRs in various immune disorders, and discusses the pathogenesis of diseases.     

The role of Toll-like receptors in immune disorders

Toll-like receptors (TLRs) play an important role in innate immunity. Individual TLRs recognise microbial components that are conserved among pathogens. Such recognition initiates necessary inflammatory immune responses and induces subsequent activation of adaptive immunity. Studies in people with polymorphisms in genes encoding TLR signalling can elucidate the relationship between TLRs and human diseases, such as infectious diseases, atherosclerosis and immunodeficiency. Indeed, accumulating data in respect to TLR signalling suggest that TLRs are closely related with the pathogenesis of autoimmune diseases. This review looks at the role of TLRs in various immune disorders, and discusses the pathogenesis of diseases.     

Role of toll-like receptors in cardiovascular diseases

The discovery and characterization of the TLR (Toll-like receptor) family has led to a better understanding of the innate immune system. The strategy of innate immune recognition is based on the detection of constitutive and conserved products of micro-organisms. However, host molecules that are released during injury can also activate TLRs. Engagement of TLRs by microbial or host-derived molecules induces the expression of pro-inflammatory cytokines, which may have both beneficial and detrimental effects on the host. In addition to being expressed in immune cells, TLRs are expressed in other tissues such as those of the cardiovascular system. In the present review, the role of TLRs in septic cardiomyopathy, viral myocarditis, atherosclerosis, ischaemia/reperfusion injury and cardiac remodelling after myocardial infarction are outlined, with attention paid to genetically modified murine models. Although much has been learned about stress-induced TLR activation in the tissues of the cardiovascular system, the role of individual TLRs in initiating and integrating homoeostatic responses within the heart remains to be defined. Accumulating evidence indicates that TLRs may play an important role in the pathogenesis of atherosclerosis, viral myocarditis, dilated cardiomyopathy, cardiac allograft rejection and sepsis-induced left ventricular dysfunction. Moreover, heart failure of diverse aetiology is also now recognized to have an important immune component, with TLR signalling influencing the process of cardiac remodelling and prognosis. In the present review, we outline the biology of TLRs as well as the current experimental and clinical evidence for the role of TLRs in cardiovascular diseases.     

Modulation of toll-like receptors by insulin

Toll-like receptors (TLRs) are first-line molecules for initiating the innate immune responses and mediating functional activation in immune effector cells. A family of 10 functional human TLRs altogether can recognize the ligands that do not exist in the host and initiate the inflammatory cascades. This triggers the production of inflammatory cytokines, chemokines, and interferons. Overactivation of innate immunity might lead to immune-mediated inflammatory disorders. Besides that, TLRs are currently viewed as active participants in the cross-communication between immunity and metabolic health. Recent data directly implicate the activation of inflammatory pathways in the pathogenesis of type 1 and type 2 diabetes, atherosclerosis, obesity, and also cancer. The following approaches to develop new TLR drugs have been undertaken: generating TLR agonists/antagonists, creating monoclonal antibody to TLRs, blocking the key molecules in the signaling pathways, down-modulating TLR signaling. In this article, we briefly review the involvement of TLRs in diseases associated with metabolic alterations, underscoring the modulation of TLRs by insulin.     

Role of Toll-like receptors in the development of sepsis

The outcome of sepsis and septic shock has not significantly improved in recent decades despite the development of numerous drugs and supportive care therapies. To reduce sepsis-related mortality, a better understanding of molecular mechanism(s) associated with the development of sepsis and sepsis-related organ injury is essential. There is increasing evidence that Toll-like receptors (TLRs) play a key role in the mediation of systemic responses to invading pathogens during sepsis. However, the role of TLRs in the development of sepsis and in sepsis-related organ injury remains debatable. In this review, we focus on the biological significance of TLRs during sepsis. Medline was searched for pertinent publications relating to TLRs, with emphasis on their clinical and pathophysiological importance in sepsis. In addition, a summary of the authors' own experimental data from this field was set in the context of current knowledge regarding TLRs. In both animal models and human sepsis, TLRs are highly expressed on monocytes/macrophages, and this TLR expression may not simply be a ligand-specific response in such an environment. The fact that TLR signaling enables TLRs to recognize harmful mediators induced by invading pathogens may be associated with a positive feedback loop for the inflammatory response among different cell populations. This mechanism(s) may contribute to the organ dysfunction and mortality that occurs in sepsis. A better understanding of TLR biology may unveil novel therapeutic approaches for sepsis.     

Basic understanding and therapeutic approaches to target toll‐like receptors in cancerous microenvironment and metastasis

Toll‐like receptors (TLRs) are transmembrane components that sense danger signals, like damage‐ and pathogen‐associated molecular pattern molecules, as receptors, and maintain homeostasis in tissues. They are mainly involved in immune system activation through a variety of mediators, which either carry out (1) elimination of pathogenic threats and redressing homeostatic imbalances or (2) contribution to the initiation and worsening of pathological conditions, including cancers. Under physiological conditions, TLRs coordinate the innate and adaptive immunity, and inhibit autoimmune disorders. In pathological conditions, such as cancer, they can present both tumor and receptor‐specific roles. Although the roles of individual TLRs in various cancers have been described, the effects of targeting TLRs to treat cancer and prevent metastasis are still controversial. A growing body of literature has suggested contribution of both activators and inhibitors of TLR signaling pathway for cancer treatment, dependent on several context‐specific factors. In short, TLRs can play dual roles with contradictory outcomes in neoplastic conditions. This hampers the development of TLR‐based therapeutic interventions. A better understanding of the interwoven TLR pathways in cancerous microenvironment is necessary to design TLR‐based therapies. In this review, we consider the molecular mechanisms of TLRs signaling and their involvement in tumor progression. Therapeutic modalities targeting TLRs for cancer treatment are discussed as well.     

Toll-like receptors in health and disease in the brain: mechanisms and therapeutic potential

The discovery of mammalian TLRs (Toll-like receptors), first identified in 1997 based on their homology with Drosophila Toll, greatly altered our understanding of how the innate immune system recognizes and responds to diverse microbial pathogens. TLRs are evolutionarily conserved type?I transmembrane proteins expressed in both immune and non-immune cells, and are typified by N-terminal leucine-rich repeats and a highly conserved C-terminal domain termed the TIR [Toll/interleukin (IL)-1 receptor] domain. Upon stimulation with their cognate ligands, TLR signalling elicits the production of cytokines, enzymes and other inflammatory mediators that can have an impact on several aspects of CNS (central nervous system) homoeostasis and pathology. For example, TLR signalling plays a crucial role in initiating host defence responses during CNS microbial infection. Furthermore, TLRs are targets for many adjuvants which help shape pathogen-specific adaptive immune responses in addition to triggering innate immunity. Our knowledge of TLR expression and function in the CNS has greatly expanded over the last decade, with new data revealing that TLRs also have an impact on non-infectious CNS diseases/injury. In particular, TLRs recognize a number of endogenous molecules liberated from damaged tissues and, as such, influence inflammatory responses during tissue injury and autoimmunity. In addition, recent studies have implicated TLR involvement during neurogenesis, and learning and memory in the absence of any underlying infectious aetiology. Owing to their presence and immune-regulatory role within the brain, TLRs represent an attractive therapeutic target for numerous CNS disorders and infectious diseases. However, it is clear that TLRs can exert either beneficial or detrimental effects in the CNS, which probably depend on the context of tissue homoeostasis or pathology. Therefore any potential therapeutic manipulation of TLRs will require an understanding of the signals governing specific CNS disorders to achieve tailored therapy.     

Toll-like receptors (TLRs) and immune disorders

Upon the invasion of pathogens, the immune system needs to mount defense responses immediately. Over the past 10 years, Toll-like receptors (TLRs) have been discovered in mammals and defined as pathogen sensors. TLRs are considered to bind directly to ligands, discriminate them immediately, and induce defense responses when appropriate. We here review microbial recognition by TLRs, downstream signaling, and the relationship of TLRs to susceptibility to infectious diseases and immune disorders. Recent reports have revealed a requirement for co-receptors in TLR responses. A TLR signaling pathway is required for protection against infectious diseases, but excessive signaling may lead to allergies, autoimmune diseases, or atherosclerosis. In humans, several deficiencies of signaling molecules downstream of TLRs, and TLR polymorphisms that affect recognition or signaling, were reported to cause immunodeficiencies. It is important to understand how TLR signaling is controlled.     

Toll-Like Receptor Expression in the Peripheral Nerve

Toll样受体(TLRs)是由进化上相对保守的蛋白家族构成的一组识别受体,是固有免疫系统的第一道防线。受到微生物配体刺激后,TLRs通过激活各种信号通路引发机体一系列防御反应。TLRs还能被内源性危险信号激活,因此推断神经退行性变也可能通过TLRs激活免疫反应。近来研究发现中枢神经系统表达各种类型的TLRs,但周围神经系统中TLRs的表达形式尚无定论。本研究结果显示,施万细胞上表达大量TLRs,主要为TLR3和TLR4。感觉神经元和运动神经元上几乎没有TLRs表达。对NF-κB信号通路的检测显示,施万细胞上所有的TLRs都是有功能的,可被细菌脂蛋白(TLR1/TLR2配体)激活,产生强烈反应。静息状态下,坐骨神经上TLRs的表达形式与施万细胞相似,主要为TLR3、TLR4和TLR7,可能在免疫监督中扮演重要角色。通过显微外科方式对坐骨神经造成急性神经退行性变后,诱导TLR1大量表达,其它TLRs的表达水平无变化。综上所述,本研究结果显示,施万细胞可能在周围神经中扮演类似中枢神经系统小胶质细胞的角色。急性神经退行性变诱导TLR表达变化,说明在分布于周围神经的TLRs在静息状态和激活状态下具有不同功能。