TLRS在介导结核分枝杆菌感染免疫反应中作用的研究进展

结核分枝杆菌(Mycobacterium tuberculosis,MTB)是结核病的致病菌,机体免疫反应在MTB的防御和致病中发挥着关键的调控作用,Toll样受体(Toll-like receptors,TLRs)是表达在哺乳动物细胞表面的一类重要的模式识别受体,调控着机体的先天免疫和获得性免疫。研究证明,TLRs是抗结核免疫反应的关键分子,参与介导了宿主对MTB的识别,本文就主要与MTB感染相关的TLRs及其在介导MTB感染免疫反应中的作用进行综述。     

TLRs与抗结核免疫

TLRs是近来在哺乳动物中发现的同源于果蝇Toll的蛋白分子,在宿主的天然免疫中具有重要的作用.最近的研究表明,TLRs是介导宿主对结核杆菌的识别及抗结核免疫反应的关键分子.目前对TLRs基因敲除小鼠的研究有望进一步揭开各个TLRs在抗结核免疫中的确切作用机制.     

TLRs与抗结核免疫

TLRs是近来在哺乳动物中发现的同源于果蝇Toll的蛋白分子，在宿主的天然免疫中具有重要的作用。最近的研究表明，TLRs是介导宿主对结核杆菌的识别及抗结核免疫反应的关键分子。目前对TLRs基因敲除小鼠的研究有望进一步揭开各个TLRs在抗结核免疫中的确切作用机制。     

Toll样受体在结核分枝杆菌致病机制中的作用研究进展

结核分枝杆菌是肺结核的致病菌,它可寄生在细胞内并长期存活.目前结核杆菌的致病机制及机体对其的免疫反应尚未完全阐明.Toll样受体属于模式识别受体,在结核杆菌宿主防御反应中具有极为重要的作用.Toll样受体作为连接天然免疫与获得性免疫的"桥梁",在机体免疫调节中的作用已愈来愈受关注.关于Toll样受体与结核杆菌的相关研究已成为生命科学领域的热点.     

Toll样受体在结核分枝杆菌致病机制中的作用研究进展

结核分枝杆菌是肺结核的致病菌,它可寄生在细胞内并长期存活.目前结核杆菌的致病机制及机体对其的免疫反应尚未完全阐明.Toll样受体属于模式识别受体,在结核杆菌宿主防御反应中具有极为重要的作用.Toll样受体作为连接天然免疫与获得性免疫的"桥梁",在机体免疫调节中的作用已愈来愈受关注.关于Toll样受体与结核杆菌的相关研究已成为生命科学领域的热点.     

Toll样受体在结核分枝杆菌致病机制中的作用研究进展

结核分枝杆菌是肺结核的致病菌,它可寄生在细胞内并长期存活.目前结核杆菌的致病机制及机体对其的免疫反应尚未完全阐明.Toll样受体属于模式识别受体,在结核杆菌宿主防御反应中具有极为重要的作用.Toll样受体作为连接天然免疫与获得性免疫的"桥梁",在机体免疫调节中的作用已愈来愈受关注.关于Toll样受体与结核杆菌的相关研究已成为生命科学领域的热点.     

Toll样受体与心血管疾病

Toll样受体(TLRs)是在自身免疫反应中起重要作用的类型识别受体家族,是心血管疾病发展与免疫系统之间的桥梁。许多遗传学研究、临床研究和基础研究发现TLRs在动脉粥样硬化、充血性心力衰竭、心肌肥厚发生、发展中起了作用,但尚有许多未知领域有待研究。     

Toll样受体与心血管疾病

Toll样受体(TLRs)是在自身免疫反应中起重要作用的类型识别受体家族,是心血管疾病发展与免疫系统之间的桥梁。许多遗传学研究、临床研究和基础研究发现TLRs在动脉粥样硬化、充血性心力衰竭、心肌肥厚发生、发展中起了作用,但尚有许多未知领域有待研究。     

Toll样受体4与动脉粥样硬化

炎症免疫反应是机体对微生物侵袭的天然防御反应，免疫细胞通过其细胞膜上的受体识别外来微生物的配体。从而启动宿主的炎症免疫反应。研究表明，动脉粥样硬化（atherosclerosis，As）是一种慢性炎症疾病，伴有免疫反应的炎症过程在As的发生和发展中起着决定性作用。但免疫反应在其中的分子生物学机制至今还未阐明。最近发现的Toll样受体（toll-like receptors，TLRs）是模式识别受体，能调节先天与获得性免疫，在抗微生物感染和识别内源性配体中起重要作用。TLRs识别内外源性配体后，启动炎性应答通路，诱导炎性因子大量产生，从而对机体组织产生保护和损伤作用。大量证据表明，TLRs在As中起着重要作用。本文就TLR4与As的相关研究作一综述。     

Toll样受体参与心肌缺血再灌注损伤的研究进展

<正>再灌注治疗在急性心肌梗死患者中应用逐渐增多,其引发的再灌注损伤日益受到人们的重视,对其发生机制进行了积极的探索研究,近年来研究发现,固有免疫的成员之一Toll样受体在心肌缺血再灌注损伤的炎症反应中起了重要作用,本文就Toll受体在心肌缺血再灌注损伤中的作用及发生机制展开综述。1 TLRs概述Toll样受体家族(TLRs)是最早被人类认识的免疫细胞的模式识别受体(PRRS),TLRs最初发现是果     

Toll-like Receptors in Systemic Lupus Erythematosus: Potential Targets for Therapeutic Intervention

Toll-like receptors (TLRs) have attracted increased attention in recent years, not only for their role in sensing conserved microbial components, but also in the realm of autoimmunity. Although TLRs are most widely known for their capacity to detect conserved motifs of infectious agents, mounting evidence indicates that these innate receptors also promote autoimmune conditions by causing uncontrolled autoinflammation as a result of chronic recognition of self. In response to the need for modern approaches to treatment of autoimmune diseases, several groups have begun investigating ways to target TLRs as new therapeutic options for autoimmune conditions. Here we discuss recent data describing advances in TLRs as therapeutic targets for treatment of autoimmune diseases, with a focus on systemic lupus erythematosus.     

Toll-like receptors and T-helper-1/T-helper-2 responses

PURPOSE OF REVIEW: Toll-like receptors (TLRs) are a family of pattern recognition receptors that are activated by specific components of microbes and certain host molecules. They constitute the first line of defense against many pathogens and play a crucial role in the function of the innate immune system. Recently, TLRs were observed to influence the development of adaptive immune responses, presumably by activating antigen-presenting cells. This has important implications for our understanding of how the host tailors its immune response as a function of specific pathogen recognition. The present review discusses the recent studies that demonstrate the role of TLRs in the regulation of adaptive T-helper-1 (Th1) and Th2 responses, and the mechanisms by which the effects are carried out. RECENT FINDINGS: Most studies have focused on the role of TLRs and components of their signaling pathways in the control of Th1-type immune responses, and on the implications for their use as antimicrobial agents, such as adjuvants in vaccines, or to treat or prevent the Th2-type dominated immune responses seen in allergies. TLR-deficient mice have been described and used to come to these conclusions. Although controversial, there is also evidence that TLRs may be important for Th2-type responses, possibly by augmenting the overall maturity of dendritic cells. SUMMARY: A greater understanding of the processes by which TLRs regulate adaptive immunity may yield not only improved ways to treat infectious diseases but also new approaches to the treatment and prevention of allergic and certain autoimmune disorders.     

Toll-like receptors and hepatitis C virus infection

BackgroundHepatitis C virus (HCV) infection is a worldwide issue. However, the current treatment for hepatitis C has many shortcomings. Toll-like receptors (TLRs) are pattern recognition receptors involved in HCV infection, and an increasing number of studies are focusing on the role of TLRs in the progression of hepatitis C.Data sourcesWe performed a PubMed search up to January 2021 with the following keywords: hepatitis C, toll-like receptors, interferons, inflammation, and immune evasion. We also used terms such as single-nucleotide polymorphisms (SNPs), susceptibility, fibrosis, cirrhosis, direct-acting antiviral agents, agonists, and antagonists to supplement the query results. We reviewed relevant publications analyzing the correlation between hepatitis C and TLRs and the role of TLRs in HCV infection.ResultsTLRs 1–4 and 6–9 are involved in the process of HCV infection. When the host is exposed to the HCV, TLRs, as important participants in HCV immune evasion, trigger innate immunity to remove the virus and also promote inflammation and liver fibrosis. TLR gene SNPs affect hepatitis C susceptibility, treatment, and prognosis. The contribution of each TLR to HCV is different. Drugs targeting various TLRs are developed and validated, and TLRs can synergize with classic hepatitis C drugs, including interferon and direct-acting antiviral agents, constituting a new direction for the treatment of hepatitis C.ConclusionsTLRs are important receptors in HCV infection. Different TLRs induce different mechanisms of virus clearance and inflammatory response. Although TLR-related antiviral therapy strategies exist, more studies are needed to explore the clinical application of TLR-related drugs.     

Toll样受体及其在抗结核感染免疫中的作用

Toll样受体(Toll-like receptors,TLR)是表达在哺乳动物细胞表面的一类重要的模式识别受体,是进化中比较保守的一个受体家族,TLR能特异地识别病原体相关分子模式,不仅在激活天然免疫中发挥着莺要的作用,而且还调节获得性免疫,是连接天然免疫与特异性免疫的主要桥梁.研究表明,TLR是介导宿主对结核杆菌的识别及抗结核免疫反应的关键分子,与抗结核感染免疫有关的主要是TLR2和TLR4.对TLR的研究有助于阐明结核病的发病机制并为其治疗提供崭新的策略.     

Role of the innate immune system in host defence against bacterial infections: focus on the Toll-like receptors

The innate immunity plays a critical role in host protection against pathogens and it relies amongst others on pattern recognition receptors such as the Toll-like receptors (TLRs) and the nucleotide-binding oligomerization domains proteins (NOD-like receptors, NLRs) to alert the immune system of the presence of invading bacteria. Since their recent discovery less than a decade ago, both TLRs and NLRs have been shown to be crucial in host protection against microbial infections but also in homeostasis of the colonizing microflora. They recognize specific microbial ligands and with the use of distinct adaptor molecules, they activate different signalling pathways that in turns trigger subsequent inflammatory and immune responses that allows a immediate response towards bacterial infections and the initiation of the long-lasting adaptive immunity. In this review, we will focus on the role of the TLRs against bacterial infections in humans in contrast to mice that have been used extensively in experimental models of infections and discuss their role in controlling normal flora or nonpathogenic bacteria. We also highlight how bacteria can evade recognition by TLRs.     

Induction of antiviral immunity requires Toll-like receptor signaling in both stromal and dendritic cell compartments

Pattern recognition by Toll-like receptors (TLRs) is known to be important for the induction of dendritic cell (DC) maturation. DCs, in turn, are critically important in the initiation of T cell responses. However, most viruses do not infect DCs. This recognition system poses a biological problem in ensuring that most viral infections be detected by pattern recognition receptors. Furthermore, it is unknown what, if any, is the contribution of TLRs expressed by cells that are infected by a virus, versus TLRs expressed by DCs, in the initiation of antiviral adaptive immunity. Here we address these issues using a physiologically relevant model of mucosal infection with herpes simplex virus type 2. We demonstrate that innate immune recognition of viral infection occurs in two distinct stages, one at the level of the infected epithelial cells and the other at the level of the noninfected DCs. Importantly, both TLR-mediated recognition events are required for the induction of effector T cells. Our results demonstrate that virally infected tissues instruct DCs to initiate the appropriate class of effector T cell responses and reveal the critical importance of the stromal cells in detecting infectious agents through their own pattern recognition receptors.     

A role for Toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells

Toll-like receptors (TLRs) are pattern recognition receptors that trigger innate immunity. In this study we investigated the expression of 10 TLRs in human naive and memory B-cell subsets. We report that in human naive B cells most TLRs are expressed at low to undetectable levels, but the expression of TLR9 and TLR10 is rapidly induced following B-cell-receptor (BCR) triggering. In contrast, memory B cells express several TLRs at constitutively high levels. The differential expression of TLR9 correlates with responsiveness to its agonist, CpG DNA. Thus, human memory B cells proliferate and differentiate to immunoglobulin (Ig)-secreting cells in response to CpG, while naive B do so only if simultaneously triggered through the BCR. The BCR-induced expression of TLRs in human naive B cells prevents polyclonal activation in a primary response, because it restricts stimulation to antigen-specific B cells. In contrast, the constitutive expression of TLRs in memory B cells allows polyclonal activation of the entire memory pool. Thus, in human B cells TLRs are downstream of BCR and play a role both in the primary response and in the memory phase.     

The dsRNA binding site of human Toll-like receptor 3

Pathogen recognition by Toll-like receptors (TLRs) initiates innate immune responses that are essential for inhibiting pathogen dissemination and for the development of acquired immunity. The TLRs recognize pathogens with their N-terminal ectodomains (ECD), but the molecular basis for this recognition is not known. Recently we reported the x-ray structure for unliganded TLR3-ECD; however, it has proven difficult to obtain a crystal structure of TLR3 with its ligand, dsRNA. We have now located the TLR3 ligand binding site by mutational analysis. More than 50 single-residue mutations have been generated throughout the TLR3-ECD, but only two, H539E and N541A, resulted in the loss of TLR3 activation and ligand binding functions. These mutations locate the dsRNA binding site on the glycan-free, lateral surface of TLR3 toward the C terminus and suggest a model for dsRNA binding and TLR3 activation.     

Immunity and tolerance to infections in experimental hematopoietic transplantation

Resistance and tolerance are two types of host defense mechanisms that increase fitness in response to fungi. Several genetic polymorphisms in pattern recognition receptors, most remarkably Toll-like receptors (TLRs), have been described to influence resistance and tolerance to aspergillosis in distinct clinical settings. TLRs on dendritic cells pivotally contribute in determining the balance between immunopathology and protective immunity to the fungus. Epithelial cells also contribute to this balance via selected TLRs converging on indoleamine-2,3-dioxygenase (IDO). Studies in experimental hematopoietic transplantation confirmed the dichotomy of pathways leading to resistance and tolerance to the fungus providing new insights on the relative contribution of the hematopoietic/nonhematopoietic compartments.     

Toll-like receptors in lymphoid malignancies: Double-edged sword

Toll-like receptors (TLRs) are the best characterized pattern recognition receptors (PRRs), which play an essential role in the recognition of invading pathogens via specific microbial molecular motifs, comprising a bridge between the innate and adaptive immune responses. Toll-like receptors expression is determined in both normal immune cells and malignant cells, with a distinctive pattern compared to each other, rendering them plausible targets for cancer therapy. Improved molecular profiling of lymphoid malignancies may give new insights into pathogenesis of these cancers and pave the way for novel therapeutic agents, including TLR agonists. In the current review, we summarize the immunopathogenic roles of TLRs in B cell and T cell lymphomas, acute lymphoblastic leukemia, multiple myeloma, and chronic lymphocytic leukemia, as well as the results of studies on TLR ligands and their future implications to manage these hematologic malignancies.