鸡Toll样受体4信号通路及在鸡沙门菌抗病研究中的应用进展

Toll样受体作为一种模式识别受体,在先天免疫中通过识别病原体相关的分子模式,诱导炎症因子和细胞因子产生,在机体对抗感染过程中发挥重要作用.Toll样受体4(toll-1ike receptor 4,TLR4)是Toll样受体家族中识别细菌脂多糖最重要的模式受体.研究表明,TLR4及其信号通路的基因变异和表达调控与沙门菌的抗性有关.本文综述了TLR4/MyD88/NF-κB信号通路及其在鸡沙门菌抗病研究中的应用,并对其进行了展望.     

Toll样或非Toll样配体佐剂研究进展

有效的疫苗含有可活化天然免疫系统的佐剂组分,从而激发抗原特异性的免疫应答.Toll样受体(toll-like receptors,TLR)是一种重要的天然识别受体,大多数疫苗佐剂都是TLR配体.少数佐剂通过其他的识别受体和信号通路,以TLR非依赖性的方式来活化天然免疫系统.非Toll样配体佐剂的作用靶点主要是近来发现的NOD样受体(Nod-like receptor,NLR)、RIG(retinoic-acid-inducible gene)样受体(RIG-like receptors,RLR)等胞内天然免疫受体.文章对Toll样或非Toll样配体作为疫苗佐剂的研究进行了综述.     

不同动物TLR7基因研究概况

Toll样受体是调控机体免疫反应的一类重要模式识别受体,不仅能识别病原微生物调控免疫应答反应,启动固有免疫机制,其引发的信号通路还能引起适应性免疫反应的活化。其中Toll样受体7(Toll-like receptor 7,TLR7)参与抗病毒免疫反应,在天然免疫中起重要作用。论文就TLR7基因的发现、不同动物单核苷酸多态性(SNP)分析、免疫调控作用研究、不同动物TLR7基因参与抗病毒作用及展望进行综述。     

TLR4与脂代谢的研究进展

Toll样受体4(TLR4)是人类最早发现的一种Toll样受体相关蛋白,普遍分布于多种免疫细胞的膜表面,通过识别脂多糖等外源性配体激活My D88依赖性和非依赖性信号通路,参与炎症反应和免疫应答。近年来,诸多学者对TLR4信号通路介导的炎症反应、脂代谢调控及其相互作用关系进行了系统研究,相关研究表明,TLR4除了在先天性免疫过程中扮演重要角色外,还参与着机体脂代谢的调节过程。文章主要通过阐述TLR4的结构、分布、配体、信号通路及其与脂代谢的相互关系来介绍TLR4的最新研究进展。     

Toll样受体及其与细菌感染性疾病关系的研究进展

Toll样受体(TLR)是一类Ⅰ型跨膜糖蛋白模式识别受体,其通过识别病原体,激活天然免疫,可诱导产生多种细胞因子,在抗感染免疫中发挥重要作用。研究表明TLR与禽类细菌感染密切相关。文章就TLR的结构、信号转导机制、识别细菌的分子机制及其与禽类细菌感染的关系进行分析,为以后应用TLR预防和诊断禽类传染性疾病奠定基础。     

禽类Toll样受体的分子进化与作用机制研究进展

Toll样受体(Toll-like receptors,TLRs)是先天免疫系统重要的模式识别受体(pattern recognition receptors,PRR).TLRs通过与病原微生物的病原相关分子模式(pathogen-associated molecular patterns,PAMPs)相结合,活化相关信号途径,引发抗病原体防御反应、炎症反应以及活化T细胞等免疫效应.目前已经识别了10个禽类Toll样受体,包括与其它脊椎动物在结构上具有高度同源以及作用模式相对保守的TLR1\6\10、2、3、4、5、7和21,以及禽类所特有的chTLR15.本文主要阐述有关禽类Toll样受体的分子进化以及独特的作用方式研究的最新进展.     

TLRs及其信号转导的研究进展

Toll样受体（Toll-like receptors,TLRs）介导着昆虫，植物和哺服动物的宿主防御反应。目前已经报道了9种哺乳动物的TLRs，其功能研究较为明确的是TLR2和TLR4。它们与配体相互作用，以不同的信号转导途径迅速介导细胞因子和炎性介质的表达。     

家禽TLR5的研究进展

Toll样受体(TLRs)是最早发现的哺乳动物天然免疫模式识别受体家族,也是研究最广泛的模式识别受体(PRRs),其研究极大地丰富了免疫生物学内涵。TLRs和其他PRRs识别病原相关分子模式(PAMPs),可以激活细胞信号通路,产生各种炎症细胞因子,趋化因子和Ⅰ型干扰素(IFNs),从而迅速触发一系列抗微生物免疫反应。文章主要讨论家禽TLR5基本结构特点、信号通路及其抗感染作用,以为家禽TLR5的深入研究提供新的科学线索。     

Toll样受体在牛体内抗原呈递细胞中的研究进展

免疫系统起着发现和消除入侵病原的作用,在哺乳动物体内它可以分为天然性免疫和获得性免疫两部分.获得性免疫可以通过B细胞和T细胞表面受体识别自身抗体和病原抗体.另一方面,天然性免疫中Toll 样受体是近年来备受关注的一种病原体识别受体, 它在固有免疫中通过对病原体相关的分子模式(PAMP) 的识别发挥作用, 通过刺激信号的级联反应导致细胞因子的产生和协同刺激因子的表达.     

体内注射鸡Toll样受体4和21的配体诱导脾脏免疫系统的基因表达

Toll样受体(TLRs)是一组保守的蛋白质,除了在先天免疫和适应性免疫反应的启动和调控中发挥重要作用,还参与病原体识别。目前,已鉴定到若干个识别不同配体的鸡TLRs,在刺激鸡对病原体产生宿主反应中发挥重要作用。然而,通过哪个TLRs对鸡免疫系统进行调节尚未明了。本试验通过分别向试验鸡肌肉注射TLR4和TLR21相应的配体脂多糖(LPS)和CpG寡聚脱氧核苷酸(ODNs),对其刺激鸡免疫反应的动力学特性进行了研究。在注射TLR配体2、6、12和24h时,可在脾脏中检测到细胞因子的相应表达。结果表明,LPS能在试验早期强烈诱导免疫系统基因表达的上调,包括IFN-γ、IL-10和IL-1β。CpG ODNs能促进MHC-Ⅱ、IFN-γ和IL-10的上调。而对CpG ODNs的应答比对LPS的应答略迟。在对LPS的反应中,IFN-α基因的表达显著增加,而在对CpG ODNs的反应中无明显变化。进一步试验将对鸡TLR激活的分子机制或应用TLR激动剂作为疫苗佐剂进行研究。     

Expression and function of Toll-like receptor 2 in canine blood phagocytes

Toll-like receptors (TLRs) are a family of highly conserved pattern recognition receptors (PRR) of mammals that participate in the activation of innate immune responses against microbial infections. Among these receptors, TLR2 is essential for the recognition of conserved structural components of bacteria, protozoa and fungi. Until now, expression of TLR2 in dogs has not been investigated. In this work we describe a partial sequence of the gene coding for canine TLR2 and show that TLR2 mRNA is constitutively expressed in canine blood PMNs. We also show that stimulation of purified PMNs with lipoteichoic acid (LTA), a ligand of TLR2, leads to the release of proinflammatory chemokine IL-8. Furthermore, TLR2 protein is easily detectable by flow cytometry on the canine peripheral blood granulocyte and monocyte cell surface, and slightly on lymphocytes. These findings suggest that, also in dogs as in humans the initial antibacterial response of PMNs could be elicited through engagement of TLR2.     

Toll样受体信号通路在两栖类中的研究进展

两栖类处于脊椎动物由水生向陆生进化的过渡阶段,进化地位重要。近年来因疾病的爆发、生境破碎化、环境污染、紫外辐射增加、人为过度捕捉和生物入侵等诸多因素引起的全球范围内两栖类种群数量锐减已引起人们的广泛关注。Toll样受体(Toll-like receptor,TLR)家族是一类从线虫到哺乳动物普遍存在的高度保守的模式识别受体(PRRs),可以识别侵入机体病原体的病原相关分子模式(PAMPs),是两栖类先天性免疫防御系统的重要组成部分。本文结合近些年国内外对两栖类TLRs的研究对两栖类TLRs结构特征、进化特点、在两栖类发育早期的差异表达特征和两栖类TLRs信号通路中相关分子的表达研究进行概述。目前对于两栖类TLRs的研究发现两栖类TLRs兼具鱼类和哺乳类TLRs的特征,并在从鱼类到两栖类到哺乳类的进化过程中,TLRs家族部分成员如TLR2的配体识别功能可能发生了一定程度的特化;在两栖类早期发育阶段,获得性免疫不够完善,以TLRs为主的先天免疫防御系统在抵御病原体的侵袭方面发挥了重要作用;在特定病原菌和病毒的胁迫下,可能激活了TLRs下游不同的途径参与两栖类对病原体的免疫应答反应。     

TLR4在妊娠异常终止中的作用机制和研究进展

Toll样受体（toll-like receptors,TLRs）作为一种病原模式识别受体在免疫反应中起着重要的作用。TLR4是最早发现的TLRs成员,它是革兰氏阴性菌胞壁成分脂多糖（lipopolysaccharide, LPS）的识别受体。LPS与TLR4在胞外结合后,通过MyD88依赖和非依赖途径引起炎症反应。TLR4在生殖道炎症反应中具有重要作用,临床上可通过对利用TLR4信号转导通路的阻断来获得治疗效果。作者概述了TLR4的分子结构、组织表达和细胞内信号转导,以及在生殖系统病变状态下的表达,在此基础上提出了TLR4在生殖临床医学应用上可能的意义。     

Expression and function of Toll-like receptors on dendritic cells and other antigen presenting cells from non-human primates

Antigen presenting cells (APCs), especially dendritic cells (DCs), play a crucial role in immune responses against infections by sensing microbial invasion through Toll-like receptors (TLRs). In this regard, TLR ligands are attractive candidates for use in humans and animal models as vaccine adjuvants. So far, no studies have been performed on TLR expression in non-human primates such as rhesus macaques. Therefore, we studied the TLR expression patterns in different subsets of APC in rhesus macaques and compared them to similar APC subsets in human. Also, expression was compared with corresponding DC subsets from different organs from mice. Here we show by semi-quantitative RT-PCR, that blood DC subsets of rhesus macaque expressed the same sets of TLRs as those of human but substantially differed from mouse DC subsets. Macaque myeloid DCs (MDCs) expressed TLR3, 4, 7 and 8 whereas macaque plasmacytoid DCs (PDCs) expressed only TLR7 and 9. Additionally, TLR expression patterns in macaque monocyte-derived dendritic cells (mo-DCs) (i.e., TLR3, 4, 8 and 9), monocytes (i.e., TLR4, 7, and 8) and B cells (i.e., TLR4, 7, 8, and 9) were also similar to their human counterparts. However, the responsiveness of macaque APCs to certain TLR ligands partially differed from that of human in terms of phenotype differentiation and cytokine production. Strikingly, in contrast to human mo-DCs, no IL-12p70 production was observed when macaque mo-DCs were stimulated with TLR ligands. In addition, CD40 and CD86 phenotypic responses to TLR8 ligand (poly U) in mo-DCs of macaque were higher than that of human. Despite these functional differences, our results provide important information for a rational design of animal models in evaluating TLR ligands as adjuvant in vivo.     

Molecular cloning and characterization of equine Toll-like receptor 9

Innate immunity relies on a series of germline-encoded pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), to detect conserved microbial components. TLR9 is typically expressed intracellularly in immune cells such as dendritic cells and recognizes unmethylated bacterial or viral cytosine-phosphate-guanine DNA (CpG-DNA). To investigate innate immune responses through TLR9 signaling pathway in horses, we cloned and characterized equine TLR9. Protein sequence analysis shows that equine TLR9 has a typically conserved cytosolic Toll/interleukin-1 receptor (TIR) domain, three leucine-rich repeat (LRR) motifs, with greater than 82% identity to human, monkey, bovine, canine, feline, porcine and ovine orthologs. Equine TLR9 mRNA expression was characterized for spleen, lymph node, and peripheral blood leukocyte samples. Flow cytometric analysis of equine TLR9 expression using a cross-reactive TLR9 mAb identified high constitutive expression of equine TLR9 in PMNs, CD4(+) and CD8(+) T-lymphocytes as well as other leukocytes; similar to human TLR9 expression. The conservation of equine TLR9 and high expression profile in leukocytes suggests that equine TLR9 is a frequent target for unmethylated CpG-DNA, an essential mechanism for the activation of innate immunity.     

Toll-like receptor expression in feline lymphoid tissues

Toll-like receptors (TLRs) are germline-encoded pattern recognition receptors (PRRs) that activate the innate immune system. While it is clear that TLRs are important in the immune response against pathogens, they may also be exploited by some pathogens. Our objective is to determine whether feline immunodeficiency virus (FIV) infection affects TLR expression or function thereby resulting in innate immune dysfunction. To this end, we cloned partial sequences for feline TLRs 1--3, 5--8, and developed real-time PCR assays to quantify feline TLRs 1--9. TLR expression was quantified in normal cat lymphoid tissues, purified lymphocyte subsets, and FIV-infected cell lines. Different expression patterns of TLRs were found in spleen, mesenteric lymph node, retropharyngeal lymph node, thymus, intestinal intraepithelial lymphocytes, and lamina propria lymphocytes. B lymphocytes, CD4+ T cells, and CD8+ T cells all expressed TLRs 2--5, 7--9; however, the relative levels of expression varied among lymphocyte phenotypes. Infection of cell lines with FIV resulted in altered TLR expression levels that differed depending on cell type. These results demonstrate that tissue distribution of TLRs is associated with the immunological role of a particular tissue, that lymphocytes may also express these 'innate immune' receptors, and that FIV infection can alter TLR expression.     

Toll-like receptor activation and expression in bovine alpha-herpesvirus infections

The involvement of Toll-like receptors (TLRs) in bovine herpesvirus types 1 (BoHV-1) and 5 (BoHV-5) infections has not been analyzed. In this study, the role of TLR signaling on virus replication was investigated. Blood leukocytes consistently express TLRs. Thus, our approach was to study in vitro the effects of agonist stimulation of TLRs expressed by peripheral blood leukocytes on BoHV-1 and BoHV-5 replication. Furthermore, the patterns of TLRs 3, 7–9 expression on virus-infected-bovine leukocytes were analyzed. Only Imiquimod (TLR7/8 agonist) showed anti-viral activity on infected MDBK cells. This is the first evidence that the timely activation of TLR7/8 signaling is effective in impairing BoHV-1 and 5 replication, thereby providing an experimental indication that Imiquimod may be a promising immune modulator. This work describes, for the first time, the expression patterns of TLRs in BoHV-1- or BoHV-5-infected-bovine leukocytes, suggesting the involvement of TLR7 and TLR9 in the recognition of these viruses.