鸡Toll样受体研究进展

Toll样受体（Tou—hkereceptors，TLRs）是天然免疫系统中一类重要的模式识别受体（Patternrecognitionreceptors，PRRs）。PRRs对病原体相关分子模式（Pathogenmolecularpatterns，PAMPs）的识别引起炎性因子、趋化因子、共刺激分子和MHC分子的表达，激发机体的免疫反应从而消除病原体的入侵。本文主要对鸡TLR家族组成及其生物学功能进行了简要的综述。     

Toll样受体研究进展

Toll-like receptors(TLRs)是存在于机体的一类重要的模式识别受体,在机体天然免疫中起着重要的作用.TLRs还是连接天然免疫和适应性免疫的桥梁.目前TLR1-9研究的较清楚和详尽.不同TLRs识别的病原体相关分子模式各不相同.TLRs介导的机体信号传导途径分为MyD88依赖性和非MyD88依赖性.多种生物TLRs已被克隆和表达,通过进化分析,脊椎动物的TLRs可被分为6大基因家族,识别相似PAMP的TLRs聚为一簇.TLRs编码序列和功能是高度保守的.     

大白猪TLR5基因新变异位点检测及其与部分免疫指标的关联分析

<正>Toll样受体（Toll-like receptor,TLRs）是动物天然免疫体系的重要成分之一,可识别病原微生物具有的保守结构分子,可检测微生物感染并触发抗菌宿主的防御反应,参与构成防御感染性疾病的第一条防线。Toll样受体5(Toll-like receptor 5,TLR5)是TLRs家族中的一个成员,TLR5可以被细菌鞭毛蛋白激活,构成机体反抗病原菌的第一线防御机构,并且对机体内部的免疫稳态影响明显,在脊椎动物中高度保守。     

TLRs及转导基因在奶牛乳房炎防控中的研究进展

<正>奶牛乳房炎防控是目前世界范围内仍未完全解决的顽疾之一。奶牛一旦发生乳房炎感染后一般多采用抗生素治疗,不仅可引起奶牛产奶量下降甚至停奶,且有可能导致牛奶中抗生素残留,危害人体健康。TLRs(Toll-like receptors)则能识别病原体的相关分子模式(PAMP),在天然免疫防御病原体中起着重要作用。TLR4是TLRs家族成员之一,能识别革兰氏阴性菌细胞壁成分中的脂多糖(LPS)和脂磷壁酸,通过信号转导,诱导促炎症因子等基因的表达,使机体产生抗病性。     

禽Toll样受体研究进展

Toll样受体家族（Toll-like receptors,TLRs）作为一种膜表面分子,是模式识别受体（pattern recognition receptors,PRRs）的主要组分,在脊椎动物和无脊椎动物中都可识别入侵的病原体相关分子模式（pathogen associated molecular patterns,PAMPs）。通过对鸡和斑胸草雀的基因组进行比对分析,发现禽中存在10种Toll样受体,其中TLR2 a、b、3、4、5和7已经证明和哺乳动物同源;有些经过基因倍增生成两个基因,TLR1La和TLR1Lb,TLR2 a和2 b;禽TLR21可能与鱼类和两栖动物的同源;禽TLR15是禽类特有的一类受体。各种禽Toll样受体在抵御各种微生物的感染过程中发挥各自重要的作用,本文就禽Toll样受体的研究进展进行简要综述。     

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。     

反刍动物Toll样受体多基因家族的分子进化及表达模式分析

为了了解Toll样受体(Toll-like receptors,TLRs)多基因家族在反刍动物中的分子进化关系及表达分析。本研究基于6个科53种反刍动物基因组，利用同源基因对反刍动物TLR1-10基因进行系统鉴定，分析其染色体定位和基因结构、进化关系、选择压力(ω),并结合转录组数据明晰TLR基因在各组织的表达模式。研究结果表明：1)反刍动物的TLR1-10均为单拷贝基因，按进化关系分为TLR1 (TLR1/6/10)、TLR2、TLR4、TLR3 (TLR3/5)、TLR7 (TLR7/8/9)亚家族。2)反刍动物10个TLR基因整体上经受了纯化选择作用(ω<1),但共有35个氨基酸位点受到强烈的正选择作用；牛科比鹿科具有更高的ω值和更高比例的正选择位点，非病毒性TLRs比病毒性TLRs具有更高的ω和更多的正选择位点，提示鹿科TLR以及病毒性的TLR受到较强的进化约束力。3)在绵羊中，10个TLRs基因在免疫组织中均有所表达，其中TLR2和TLR9在外周血单个核细胞(PBMC)中存在高度表达。结果提示，反刍动物TLRs基因家族在进化水平上是相对保守的，均受到强烈的纯化选择作用，...     

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.     

Toll样受体的研究进展

Toll样受体(toll-like receptor,TLR)是存在于机体内的一类重要的模式识别受体,在机体天然免疫中起重要作用,可识别一种或多种特定的微生物病原体及其产物共有的高度保守的分子结构,即病原相关分子模式(pathogen associated molecular pattern,PAMP),启动针对入侵病原体的早期应答,诱发获得性免疫反应。对TLRs家族的研究有助于明确病原体被机体识别的本质,有助于阐明天然免疫及炎症反应机制,为免疫系统失调所致疾病的治疗提供新的思路,为新型疫苗(如DNA疫苗)和免疫调节剂的研发提供新的理论依据。     

TLRs基因家族在鸭法氏囊中的表达模式及分子进化分析

旨在探究TLRs基因家族(toll-like receptors,TLRs)在鸭法氏囊中的表达情况和功能差异。本研究利用qRT-PCR检测鸭法氏囊胚后发育中TLRs基因家族的表达情况,对表达模式进行聚类分析,并分别构建了TLRs启动子区和编码区的系统进化树。结果显示,TLR2a在鸭法氏囊2周龄(W2)和6周龄(W6)时期的表达水平显著高于4周龄(W4)时期(P0.05),其余TLRs各成员在鸭法氏囊胚后发育各阶段的表达差异不显著(P0.05);TLR1a、TLR2a、TLR2b以及TLR3、TLR5、TLR15具有相似的表达模式;在编码区进化树上TLR1a、TLR1b、TLR2a、TLR2b聚为一支,与TLR15距离较近,TLR3和TLR5在同一分支上,TLR4和TLR21为单独两个分支,TLR21与其他TLRs成员距离最远;而TLRs基因家族启动子区进化树没有明显规律。结果提示,TLRs家族成员可能不参与鸭法氏囊胚后发育调控过程;TLR2a和TLR2b,以及TLR3、TLR5和TLR15可能具有相似功能,TLR1a和TLR1b虽然具有较高的序列相似性,但可能在进化中出现了功能分化。TLRs表达模式与启动子区序列进化无明显联系。     

Expression and function of TLR2, TLR4, and Nod2 in primary canine colonic epithelial cells

The gut maintains a delicate balance between the downregulation of inflammatory reactions to commensal bacteria and the capacity to respond to pathogens with vigorous cellular and humoral immune responses. Intestinal epithelial cells, including colonic epithelial cells (CECs) possess many properties of cells of the innate immune system, in particular the ability to recognize and respond to microbial antigens. Recognition of microorganisms by CECs is based upon their recognition of signature molecules, called microbe-associated molecular patterns (MAMP), by pattern recognition receptors (PRR) including membrane toll-like receptors (TLR) and cytosolic Nod2, an intracellular counterpart of TLRs. The purpose of this study was to determine whether primary CECs from normal dogs express a functional TLR2, TLR4, and Nod2 and whether they are regulated by inflammatory mediators. We show that canine primary CECs express TLR2, TLR4, and Nod2 that can be modulated in response to their respective MAMPs, lipopolysaccharides (LPS) or peptidoglycans (PGN). Furthermore, we demonstrate that these receptors are functional as evidenced by the induction of cytokine gene expression in response to LPS or PGN.     

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。     

Characterization of toll-like receptors 1–10 in spotted hyenas

Previous research has shown that spotted hyenas (Crocuta crocuta) regularly survive exposure to deadly pathogens such as rabies, canine distemper virus, and anthrax, suggesting that they have robust immune defenses. Toll-like receptors (TLRs) recognize conserved molecular patterns and initiate a wide range of innate and adaptive immune responses. TLR genes are evolutionarily conserved, and assessing TLR expression in various tissues can provide insight into overall immunological organization and function. Studies of the hyena immune system have been minimal thus far due to the logistical and ethical challenges of sampling and preserving the immunological tissues of this and other long-lived, wild species. Tissue samples were opportunistically collected from captive hyenas humanely euthanized for a separate study. We developed primers to amplify partial sequences for TLRs 1–10, sequenced the amplicons, compared sequence identity to those in other mammals, and quantified TLR expression in lymph nodes, spleens, lungs, and pancreases. Results show that hyena TLR DNA and protein sequences are similar to TLRs in other mammals, and that TLRs 1–10 were expressed in all tissues tested. This information will be useful in the development of new assays to understand the interactions among the hyena immune system, pathogens, and the microbial communities that inhabit hyenas.     

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-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 expression in the nervous system of bovine alpha-herpesvirus-infected calves

In this study, the expression levels of viral Toll-like receptors (TLRs) in the nervous system of bovine herpesvirus type 5 (BoHV-5)-infected calves were investigated. A significant increase in the expression of TLRs 3 and 7–9 was found in the anterior cerebral cortex during acute infection and viral reactivation. In the trigeminal ganglia, only TLR9 expression was significantly affected. The magnitude of the increase was lower in BoHV-1-infected calves, suggesting that a restricted immune response might protect against exacerbated inflammatory responses in the brain. This work describes, for the first time, the involvement of TLRs 3 and 7–9 in the recognition of BoHV in the bovine nervous system, indicating that the expression of these receptors might be associated with the development of neurological disease. Modulation of the signalling pathways mediated by TLRs might provide an effective approach to control the neuro-immune response to BoHV-5, which may be responsible for neurological lesions.     

Characterization of two key molecules of teleost innate immunity from rainbow trout (Oncorhynchus mykiss): MyD88 and SAA

Toll-like receptors (TLR) are relevant for piscine innate immunity. TLR activation recruits several downstream factors regulating the expression of immunorelevant genes. We have characterized two key factors of innate immunity from rainbow trout: MyD88 as an adaptor protein interacting directly with TLRs, and serum amyloid A as an effector molecule induced by the activated Toll-like receptor signaling cascade.Both factors share a remarkable high degree of structural conservation with their mammalian orthologs suggesting that innate immune defense mechanisms may also functionally be conserved between fish and mammals.