广谱模式识别分子To11-like receptor 2的研究进展

TLR－2（toll-like receptor 2,TLR-2)是哺乳动物TLRs(Toll-like receptors,TLRs)家族的一员,作为细胞表面的天然受体蛋白,主要参与病原微生物产物的识别及炎症信号传导,介导天然抗感染免疫,最后又发现其参与机体对非感染因子所致炎性组织损伤的识别,通过对TLR－2参与的识别和细胞内信号传导机制的研究,可为深入探讨抵卸微生物感染的机制,对自身正常与非正常组织的提供新的思路。     

TLRs与同种异型移植排斥

Toll样受体(Toll-like receptors,TLRs)是一类在机体识别、清除入侵病原微生物免疫过程中起重要作用的受体.除此之外,新近的研究表明TLRs还参与同种异型移植过程中的排斥反应.本文就TLRs的这一进展进行了综述,内容包括TLRs的结构、功能和信号通路,TLRs与无菌性炎症,以及TLRs与皮肤、内脏移植排斥.     

Toll样受体9及其与动物疾病的研究进展

Toll样受体(Toll-like receptors,TLRs)是免疫细胞表面的识别受体,参与病原相关分子模式(pathogen-associated molecular patterns,PAMPs)的识别,包括微生物鞭毛、肽聚糖、脂多糖、 CpG基序、单链和双链RNA等.从而诱导机体的防御系统,如屏障、杀菌、吞噬作用以及细胞因子等.TLR9是TLRs家族成员之一,作为细胞表面的天然模式识别受体,其主要参与病原体CpG基序激活免疫细胞的信号转导,引起大量炎性因子的产生,从而在天然抗感染免疫以及联系天然免疫和获得性免疫中发挥重要作用.     

TLRs与肿瘤增殖和侵袭

Toll样受体(Toll-like receptors,TLRs)是参与天然免疫应答的一类重要分子,是机体抵抗病原微生物感染以及抗肿瘤的第一道防线。TLRs主要表达于免疫细胞表面,促进炎症因子的合成与释放,引发炎症反应。近年来发现TLRs在肿瘤组织中亦有表达,不同细胞表面表达的TLRs可能对肿瘤细胞产生不同的作用。在免疫细胞表面表达的TLRs可能介导肿瘤的免疫逃逸,同时也具有抗肿瘤作用,而肿     

Toll样受体-9的研究进展

Toll样受体-9(Toll-like receptor 9,TLR9)是哺乳动物TLRs家族中一员,作为细胞表面的天然模式识别受体,主要参与免疫刺激序列(CpG序列)激活免疫细胞的信号传导,从而在天然抗感染免疫及联系天然免疫和获得性免疫中发挥重要作用。通过对TLR9-CpG作用通路的研究,将促进天然免疫机制研究的进一步深入,有利于解决诸如:CpG佐剂、DNA疫苗、CpG抗感染、抑制肿瘤、预防过敏反应等实际应用过程中存在的问题。     

Toll样受体与适应性免疫

TLRs作为固有免疫系统的模式识别受体之一,识别PAMP这一多种微生物共有分子,在固有免疫中占据重要地位。此外,TLRs又以多种机制参与适应性免疫的调节。TLRs调节作用发挥的正常与否,直接关系到适应性免疫反应的结局。对TLRs的深入研究可以为感染和肿瘤等疾病的治疗开辟新的途径。     

Toll样受体与适应性免疫

TLRs作为固有免疫系统的模式识别受体之一,识别PAMP这一多种微生物共有分子,在固有免疫中占据重要地位.此外,TLRs又以多种机制参与适应性免疫的调节.TLRs调节作用发挥的正常与否,直接关系到适应性免疫反应的结局.对TLRs的深入研究可以为感染和肿瘤等疾病的治疗开辟新的途径.     

Toll样受体与Th1和Th2型免疫应答

Toll样受体是广泛表达在哺乳动物细胞表面的跨膜信号传导受体,其通过识别多种类型的病原体相关分子模式及一些内源性配体,激活天然免疫系统,同时通过诱导树突状细胞分化成熟,调控获得性免疫反应的建立。大多数TLRs的配体可诱导机体产生Th1型免疫应答,然而在某些条件下也可导致Th2型免疫应答的发生。弄清TLRs参与调节Th0分化的机制,可为今后在感染免疫、自身免疫、超敏反应等方面进行深入研究及相关疾病的治疗提供新的切入点。     

Toll样受体介导的抗病毒感染效应及其机制

Toll样受体(Toll Like Receptors,TLRs)在天然免疫中发挥着重要的作用。近年,越来越多的证据表明TLRs也参与了天然免疫系统对病毒的识别,同时它在病毒感染及其转归中也扮演了重要的角色。TLR3、TLR4、TLR7、TLR8、TLR9等TLRs可识别特异性蛋白、DNA和RNA等病毒源性分子,启动胞内抗病毒信号传导机制,通过一系列转接蛋白和转录因子,介导了以干扰素反应为主要机制的固有免疫防御机制,同时也参与调控针对病毒的特异性免疫应答。此外,某些病毒具有针对TLRs的免疫逃逸机制。     

结肠癌组织中Toll样受体4基因表达

肿瘤细胞表面存在Toll样受体（Toll—like receptor,TLR）,它有10余个家族成员,属于I型跨膜蛋白,可通过识别相关病原的分子模式及某些内源性配体引发信号传导和炎症介质释放。研究证实Toll样受体4（TLR-4）可介导肿瘤细胞的免疫逃逸和浸润功能。本文应用实时荧光定量PCR（RealtimePCR）检测结肠癌及癌旁组织中TLR-4 mRNA水平,为TLR-4基因表达与结肠癌发生、发展、浸润、转移的关系研究提供资料。     

Rapid and inexpensive real-time PCR for genotyping functional polymorphisms within the Toll-like receptor -2, -4, and -9 genes

The discovery of the human Toll-like receptors (TLRs) and the recognition of their pivotal role in sensing microbial pathogens during the last 5 years have resulted in a renewed appreciation of innate immunity. Due to their central role in both, triggering innate immunity as well as linking innate and adaptive immunity, genetic variations within the TLR genes, known to be associated with a variety of infectious diseases, are currently of great interest. Several single nucleotide polymorphisms (SNPs) within TLR genes have been described and seem to be associated with susceptibility to inflammatory diseases. However, methods for genotyping SNPs within the TLR genes, e.g. direct sequencing or polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) analysis, are time-consuming. In this work, we report novel real-time PCR methods for genotyping five TLR SNPs within TLR-2, TLR-4 and TLR-9 that have been associated with various diseases using fluorescence labeled hybridization probes and the LightCycler instrument. In addition, we provide protocols employing a standard Taq polymerase in order to reduce substantially the costs for real-time PCR.     

Toll样受体调节中性粒细胞免疫作用的研究进展

Toll样受体（TLR）是固有免疫系统中特异的I型跨膜受体及病原模式识别受体。TLR能特异地识别病原体相关分子模式（PAMP）,构成机体抵御病原微生物的第一道防线,因而在固有免疫系统中发挥重要作用,而且TLR还能调节适应性免疫,是连接固有免疫和适应性免疫的桥梁。中性粒细胞（PMN）是机体最重要的炎性细胞,在固有免疫中扮演着十分重要的角色,对炎症的发生、发展及转归起了关键的作用。作为重要受体的TLR能诱导PMN的生存与活化,在急性炎症反应、细胞信号转导和细胞凋亡中起着重要作用。     

Toll-like receptor (TLR) 4 polymorphism Asp299Gly is not associated with disease course in Dutch sarcoidosis patients

The aetiology of sarcoidosis, a systemic disorder characterized by the formation of non-caseating granulomas in variable organs, remains enigmatic. Clarification is hampered by heterogeneity in disease phenotypes and course, due partly to the influence of a variety of genetic and environmental factors. Multiple studies have pointed towards bacteria as possible causative agents. Toll-like receptors (TLR) are innate immunity receptors important in the immune response against pathogens. TLR-4, together with CD14 and MD-2, is an essential receptor for the recognition of lipopolysaccharide (LPS), unique to the cell wall of Gram-negative bacteria. Recently, an association between TLR-4 polymorphism Asp299Gly, leading to a change in the extracellular domain of the receptor and possible hyporesponsiveness to LPS, and a chronic course of sarcoidosis was found in German patients. In the present study this polymorphism was genotyped in 156 Dutch sarcoidosis patients and 200 healthy Dutch controls using dual-labelled fluorescent oligonucleotides. No differences were found in allelic distributions between patients and controls (P = 0.79) or within the different clinical entities of the sarcoidosis group (P = 0.44). Importantly, there were no differences between the Dutch and German sarcoidosis patients (P = 0.62). However, the allelic distribution of the Asp299Gly polymorphism differed significantly between both control groups (P = 0.04). This study highlights the importance of testing a reported gene association in a distinct population when performing genetic association studies.     

Influence of Toll-like receptor 2 and interleukin 10 on the intestinal epithelial barrier and their roles in inflammatory bowel disease

Different polymorphisms in key genes of innate and adaptive immunity disrupt the intestinal host-microbiotic balance in inflammatory bowel disease (IBD). In most cases these alterations affect the maintenance of the intestinal epithelium. Because of this, actions taken in order to reinforce or help intestinal epithelium recovery can provide benefits to idiopathic illnesses such as IBD. With this in mind, several studies support the idea that actions derived from the Toll-like receptor (TLR) 2 of the epithelial cells may help to maintain the epithelial barrier. However, in inflammatory conditions TLR-2 disappears from the intestinal epithelium and acquires a pivotal role in dendritic cells. In this event, the interleukin (IL)-10 production by sub-epithelial dendritic cells mediated by TLR-2 activation, thus leading to T-reg phenotypes in the lamina propria, may favour the recovery from epithelial damage. Therefore, the TLR-2/IL-10 axis can help to reinforce and recover the epithelial lining in IBD. In this way, several data suggest that early epithelial repair diminishes the antigen load reaching the lamina propria, which reduces inflammation and improves therapeutic performance. However, there is currently a lack of knowledge regarding molecular regulation of epithelial barrier by TLR-2 and IL-10.     

A frequent toll-like receptor (TLR)-2 polymorphism is a risk factor for coronary restenosis

Restenosis is a major problem for patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Inflammatory processes and genetic factors have been suggested to be involved in the pathogenesis of both atherosclerosis and restenosis. The recently discovered family of Toll-like receptors (TLRs) consists of molecules that initiate signaling after host-pathogen interactions. Recently it has been shown that the TLRs are involved in the development and progression of atherosclerosis by interfering with lipid metabolisms and by mediating inflammation. TLR-2 is a key innate immunity receptor for sensing both endogenous inflammatory mediators and ligands of several microbial pathogens postulated to be involved in atherosclerosis. A frequent single nucleotide polymorphism (SNP) for the TLR-2 gene, resulting in a non-functional receptor, has been described. By genotyping two independent groups of patients receiving PTCA, followed by stent implantation in one group, we found a significantly enhanced frequency of the TLR-2 Arg753Gln SNP in patients with restenosis as compared to those without restenosis (PTCA: 7.21 versus 2.45%, P=0.014; PTCA/stent: 6.86 versus 1.53%, P=0.013). In contrast, a common TLR-4 SNP was similarly distributed among the patient groups investigated. We furthermore compared the frequency of both SNPs in the patients with an age-matched group of individuals without atherosclerosis and found a trend towards a lower frequency of the TLR-4 SNP in the atherosclerotic group (PTCA: 5.58; PTCA/stent: 3.85 versus 7.14%). We conclude that in restenosis a functional TLR-2 is protective and potentially involved in a reaction pattern preventing restenosis. Screening for the TLR-2 Arg753Gln SNP may be of importance for stratifying a patients risk and for preventive and therapeutic measures.L. Hamann and A. Gomma contributed equally to this work     

胚胎期脂多糖暴露可通过钟样受体4引起出生后多巴胺能神经元减少

目的 观察钟样受体4(TLR-4)在胚胎期脂多糖 (LPS) 暴露引起的出生后个体脑内多巴胺 (DA) 能神经元减少中的作用.方法 TLR-4 突变型C57BL/10ScNCr小鼠和野生型C57BL/10ScSn小鼠各15只,在妊娠期第10.5天给小鼠腹腔注射LPS或肽聚糖(PDG),出生后4月龄时收集大脑组织标本(n=5),通过免疫组织化学染色和体视学技术定量DA能神经元和小胶质细胞数量,高效液相色谱法测定DA及其代谢物水平,免疫荧光法结合流式细胞术测定TNF-α和IL-1β蛋白水平.结果 出生前接触过LPS的4月龄C57BL/10ScSn小鼠,与注射生理盐水的对照小鼠比较,黑质DA能神经元减少(25.3±2.1)%,纹状体DA含量降低(33.5±5.0)%,黑质小胶质细胞数量增加(294±24)%,黑质和纹状体TNF-α和IL-1β蛋白水平也明显增高;但是出生前接触过LPS的TLR-4突变型C57BL/10ScNCr小鼠脑内无相应变化.出生前接触过TLR-2配体PDG的4月龄C57BL/10ScNCr 和C57BL/10ScSn小鼠均出现脑内DA能神经元减少和免疫炎症改变.结论 胚胎期接触LPS可通过TLR-4引起出生后个体脑内DA能神经元减少.     

The long pentraxin PTX3 as a prototypic humoral pattern recognition receptor: interplay with cellular innate immunity

Summary:  The innate immune system consists of a cellular arm and a humoral arm. Components of humoral immunity include diverse molecular families, which represent functional ancestors of antibodies. They play a key role as effectors and modulators of innate resistance in animals and humans, interacting with cellular innate immunity. The prototypic long pentraxin, pentraxin 3 (PTX3), represents a case in point of this interplay. Gene targeting of this evolutionarily conserved long pentraxin has unequivocally defined its role at the crossroads of innate immunity, inflammation, matrix deposition, and female fertility. Phagocytes represent a key source of this fluid-phase pattern recognition receptor, which, in turn, facilitates microbial recognition by phagocytes acting as an opsonin. Moreover, PTX3 has modulatory functions on innate immunity and inflammation. Here, we review the studies on PTX3 which emphasize the complexity and complementarity of the crosstalk between the cellular and humoral arms of innate immunity.     

Drosophila scavenger receptor CI is a pattern recognition receptor for bacteria.

One hallmark of innate immunity apparently conserved from primitive life forms through to humans is the ability of the host to recognize pathogen-associated molecular patterns (PAMPs). Since macrophage pattern recognition receptors are not well defined in Drosophila, we set out to identify such receptors. Our findings reveal that Drosophila macrophages express multiple pattern recognition receptors and that the Drosophila scavenger receptor, dSR-CI, is one such receptor capable of recognizing both gram-negative and gram-positive bacteria, but not yeast. Our data indicate that scavenger receptor bacterial recognition is conserved from insects to humans and may represent one of the most primitive forms of microbial recognition.     

Human beta-defensins and toll-like receptors in the upper airway

BACKGROUND: Measurement of innate markers in nasal mucosa, tonsils and adenoids might lead to new views about the role of innate immunity in the upper airway. In this study, the expression of human beta-defensins (HBD) 2 and 3 and toll-like receptors (TLR) 2 and 4 in various upper airway diseases was investigated. METHODS: Surgical samples from patients with tonsillar disease (n = 18), hypertrophic adenoids (n = 10) and sinonasal disease (n = 30) (chronic sinusitis, nasal polyps, turbinate mucosa as controls) were investigated by immunohistochemistry. Quantification of HBD-2 and 3 mRNA, TLR-2 and 4 mRNA expression was performed by real-time polymerase chain reaction (PCR). RESULTS: Immunohistochemistry revealed a strong expression of HBD-2 in tonsillar tissue. Quantification of HBD-2 and HBD-3 mRNA showed a more than tenfold higher expression in tonsillar tissue than in adenoids, whereas in nasal biopsies, only negligible defensin expression could be measured. No significant differences were found for TLR-4 between the various tissues, whereas TLR-2 expression in adenoids was significantly lower compared with other tissues. CONCLUSION: These results demonstrate a strong defensin expression in tonsillar tissue compared with nasal and paranasal mucosa and adenoids. Toll-like receptor expression in all these tissues illustrates a possibly important immunological sentinel function of upper airway mucosa.