猪源Toll样受体家族(TLRs)及其在抗病育种中的应用

Toll样受体(toll like receptors, TLRs)作为模式识别受体,不仅能够对机体特异性配体进行识别,并通过多种信号传导通路(由髓样分化蛋白88或由β-干扰素TLR结构域衔接蛋白介导)启动信号传导继而引发特异性的免疫应答,同时还在一些由支原体、病毒、细菌等感染引起的免疫应答过程中发挥了重要的调控功能。因为其重要的免疫调控作用,Toll样受体家族已成为近些年研究的热点,对畜禽抗病育种工作也具有重要的科学意义和应用前景。文章综述了猪源TLRs的种类、功能、遗传变异以及介导的信号通路,并重点介绍了猪源TLRs在抗病育种中的应用,旨在为猪Toll样受体家族基因功能研究及有效遗传标记的筛选提供参考依据。     

髓样分化因子MyD88与天然免疫系统中Toll样受体的关系

髓样分化因子（myeloid differentiation factor88,MyD88）是Toll样受体（Toll-like receptors,TLRs）信号通路中的一个关键的转接分子,属于死亡结构域（death domain）家族和Toll/IL-1R家族成员,从Toll受体与MyD88的结构、基本功能及其所介导的信号通路进行综述。     

斜纹夜蛾Toll受体基因的全基因组分析及其在杀虫剂抗性中的作用

利用公布的斜纹夜蛾基因组对TLRs基因进行全基因组分析,应用生物信息学工具分析斜纹夜蛾TLRs家族基因成员在鳞翅目害虫TLRs基因家族中的进化关系、组织表达特异性,结合转录组数据对农药反应敏感的TLRs进行基因表达及其调控网络进行分析,分析斜纹夜蛾Toll受体基因在杀虫剂抗性中的作用.结果表明:共分析出了7个TLRs基因,斜纹夜的TLRs家族基因与棉铃虫TLRs家族基因同源性较高.7个基因中的1个基因SLTLR3在肠道中高度表达,有5个TLRs基因对农药处理反应敏感.对农药反应敏感的TLRs进行基因表达和其网络进行分析,只发现了1个TLRs(SLTLR7)和其他30个基因之间的存在共表达关系,这些基因主要涉细胞表面受体信号途径、细胞定位、信号传导、细胞调控过程、生物调控过程.     

Toll受体及其配体Spatzle研究进展

Toll是一种与脊椎动物白介素-1受体同源的一种跨膜蛋白,它的首次发现是在果蝇胚胎发育背腹轴分化过程中的作用。同时Toll作为一种病原识别受体,在固有免疫中通过对病原体相关的分子模式的识别发挥作用,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。Spatzle作为无脊椎动物发育中的神经生长样信号传导因子新家族中的一员,是Toll的重要配体,在这两条通路中,通过不同的激活途径与Toll结合,诱导信号的产生。     

Toll样受体及其对水生动物疾病调控作用的研究进展

Toll样受体(Toll-like receptors,TLRs)是近年来倍受关注的一类模式识别受体(pattern recognition receptors,PRRs),在病原识别、介导机体免疫反应中发挥着重要作用。本研究对Toll样受体的发现、种类、结构、分布、配体及其信号转导途径与功能、在水生动物疾病调控中的作用进行了概述,以期进一步了解TLRs在水生动物疾病中所起的关键作用。     

Toll样受体在鱼类中的研究进展

Toll样受体是鱼类Toll信号传导途径的一个重要组成成员,对激活鱼类机体对入侵病原微生物的先天免疫应答起着十分重要的作用。对鱼类Toll样受体的结构、组织分布、功能及Toll信号传导途径进行了概述,并对鱼类Toll样受体的研究前景进行展望。     

水稻干旱胁迫相关转录因子研究进展

转录因子由于其在植物干旱信号传导过程中的关键调控作用,在水稻抗旱育种中发挥着特别重要的作用。综述了目前已经克隆的水稻干旱相关转录因子的调控机制、在水稻干旱胁迫中的作用和它们在水稻中表达情况。     

水稻干旱胁迫相关转录因子研究进展

转录因子由于其在植物干旱信号传导过程中的关键调控作用,在水稻抗旱育种中发挥着特别重要的作用。综述了目前已经克隆的水稻干旱相关转录因子的调控机制、在水稻干旱胁迫中的作用和它们在水稻中表达情况。     

拟南芥韧皮部防卫反应转录调控与小麦抗蚜虫机制

植物在受蚜虫侵袭时,乙烯或茉莉酸信号与MYB转录因子调控韧皮部防卫反应,凝集素类韧皮部蛋白(PP)与葡聚糖合酶(GSL)催化生成的胼胝质堵塞筛管细胞壁和筛孔,妨碍蚜虫刺吸韧皮部。根据笔者在拟南芥上的研究,韧皮部防卫反应由转录因子AtMYB44与乙烯信号调控,AtMYB44直接作用于乙烯信号传导调控因子EIN2,启动EIN2基因表达,EIN2转而调控韧皮部防卫反应和对桃蚜的抗性。与拟南芥相比,普通小麦基因组容量超出120多倍,不同基因家族成员冗余程度很高,功能复杂,多种机制交叉作用,影响抗虫防卫反应。小麦编码MYB、GSL和凝集素及其受体蛋白的73、22和50种基因已有全长序列克隆,哪些基因参与小麦针对蚜虫的韧皮部防卫反应以及它们与乙烯或茉莉酸信号的功能关系等问题,目前还不清楚。通过信号传导抑制剂药理学试验与基因沉默效应,鉴定参与小麦抗蚜作用的乙烯或茉莉酸信号传导因子;使用基因沉默、过表达以及荧光蛋白激光共聚焦检测技术,鉴定受乙烯或茉莉酸调控并对小麦抗蚜有调控功能的MYB、PP和GSL种类;通过染色质免疫沉淀等试验,研究MYB对PP和GSL基因表达直接或间接的调控作用,可以阐释小麦抗蚜防卫反应转录调控与信号传导的关键环节。     

Toll样受体在家畜繁殖性疾病中的作用

Toll样受体是天然免疫系统中的一种重要模式识别受体,可选择性识别病原微生物而启动天然免疫,在宿主天然免疫和获得性免疫中具有重要作用。此外,大量研究表明,Toll样受体基因的多态性与多种动物的细菌、病毒和寄生虫性疾病密切相关,说明通过Toll样受体基因的研究可为动物分子标记辅助选育研究提供依据。本文就Toll样受体家族的基本情况及其在家畜繁殖病理中的主要作用进行了综述。     

Toll-like receptor signaling pathways

Members of the Toll-like receptor (TLR) family recognize conserved microbial structures, such as bacterial lipopolysaccharide and viral double-stranded RNA, and activate signaling pathways that result in immune responses against microbial infections. All TLRs activate MyD88-dependent pathways to induce a core set of stereotyped responses, such as inflammation. However, individual TLRs can also induce immune responses that are tailored to a given microbial infection. Thus, these receptors are involved in both innate and adaptive immune responses. The mechanisms and components of these varied responses are only partly understood. Given the importance of TLRs in host defense, dissection of the pathways they activate has become an important emerging research focus. TLRs and their pathways are numerous; Science's Signal Transduction Knowledge Environment's TLR Connections Map provides an immediate, clear overview of the known components and relations of this complex system.     

Enhanced dendritic cell antigen capture via toll-like receptor-induced actin remodeling

Microbial products are sensed through Toll-like receptors (TLRs) and trigger a program of dendritic cell (DC) maturation that enables DCs to activate T cells. Although an accepted hallmark of this response is eventual down-regulation of DC endocytic capacity, we show that TLR ligands first acutely stimulate antigen macropinocytosis, leading to enhanced presentation on class I and class II major histocompatibility complex molecules. Simultaneously, actin-rich podosomes disappear, which suggests a coordinated redeployment of actin to fuel endocytosis. These reciprocal changes are transient and require p38 and extracellular signal-regulated kinase activation. Thus, the DC actin cytoskeleton can be rapidly mobilized in response to innate immune stimuli to enhance antigen capture and presentation.     

Decoding the patterns of self and nonself by the innate immune system

The innate immune system evolved several strategies of self/nonself discrimination that are based on the recognition of molecular patterns demarcating infectious nonself, as well as normal and abnormal self. These patterns are deciphered by receptors that either induce or inhibit an immune response, depending on the meaning of these signals.     

Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response

In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1-hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis. We also observed that sera from African-American individuals, known to have increased susceptibility to tuberculosis, had low 25-hydroxyvitamin D and were inefficient in supporting cathelicidin messenger RNA induction. These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection.     

Expression of Chicken Toll-Like Receptors and Signal Adaptors in Spleen and Cecum of Young Chickens Infected with Eimeria tenella

Toll-like receptors （TLRs） are a group of highly conserved molecules which initiate the innate immune response to pathogens by recognizing structural motifs of microbes. Understanding the changes in chicken Toll-like receptors （ChTLRs） and signal adaptors expression that occur with Eimeria tenella infection will help to elucidate the molecular basis of immune control of coccidiosis caused by Eimeria. The present study detected the dynamic changes in the expression of ChTLRs and associated signal adaptors in the spleen and cecum ofE. tenella-infected chickens during the early stage of infection. The results showed that the expression peak for ChTLRs, MyD88 and TRIF occurred at 12 h post-infection （hpi）, ChTLR3, ChTLRI 5 and MyD88 mRNA expression in the spleen ofE. tenella infected chickens were significantly higher （P〈0.05） than that of negative control chickens, and there were similar tendencies of these molecules expression in the cecum and spleen of E. tenella-infected chickens. The expression of MyD88 was upregnlated at four time points in the cecum of E. tenella-infected chickens. The results of this study indicate that ChTLR3, ChTLR15 and MyD88 play a role in young chickens infected with E. tenella.     

Induction of direct antimicrobial activity through mammalian toll-like receptors

The mammalian innate immune system retains from Drosophila a family of homologous Toll-like receptors (TLRs) that mediate responses to microbial ligands. Here, we show that TLR2 activation leads to killing of intracellular Mycobacterium tuberculosis in both mouse and human macrophages, through distinct mechanisms. In mouse macrophages, bacterial lipoprotein activation of TLR2 leads to a nitric oxide-dependent killing of intracellular tubercle bacilli, but in human monocytes and alveolar macrophages, this pathway was nitric oxide-independent. Thus, mammalian TLRs respond (as Drosophila Toll receptors do) to microbial ligands and also have the ability to activate antimicrobial effector pathways at the site of infection.     

New paradigms in type 2 immunity

Nearly half of the world's population harbors helminth infections or suffers from allergic disorders. A common feature of this population is the so-called "type 2 immune response," which confers protection against helminths, but also promotes pathologic responses associated with allergic inflammation. However, the mechanisms that initiate and control type 2 responses remain enigmatic. Recent advances have revealed a role for the innate immune system in orchestrating type 2 responses against a bewildering array of stimuli, from nanometer-sized allergens to 20-meter-long helminth parasites. Here, we review these advances and suggest that the human immune system has evolved multiple mechanisms of sensing such stimuli, from recognition of molecular patterns via innate immune receptors to detecting metabolic changes and tissue damage caused by these stimuli.     

Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria

The enormous number of commensal bacteria in the lower intestine of vertebrates share abundant molecular patterns used for innate immune recognition of pathogenic bacteria. We show that, even though commensals are rapidly killed by macrophages, intestinal dendritic cells (DCs) can retain small numbers of live commensals for several days. This allows DCs to selectively induce IgA, which helps protect against mucosal penetration by commensals. The commensal-loaded DCs are restricted to the mucosal immune compartment by the mesenteric lymph nodes, which ensures that immune responses to commensal bacteria are induced locally, without potentially damaging systemic immune responses.     

Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex

Cytokine signaling is thought to require assembly of multicomponent signaling complexes at cytoplasmic segments of membrane-embedded receptors, in which receptor-proximal protein kinases are activated. Indeed, CD40, a tumor necrosis factor receptor (TNFR) family member, forms a complex containing adaptor molecules TRAF2 and TRAF3, ubiquitin-conjugating enzyme Ubc13, cellular inhibitor of apoptosis proteins 1 and 2 (c-IAP1/2), IkappaB kinase regulatory subunit IKKgamma (also called NEMO), and mitogen-activated protein kinase (MAPK) kinase kinase MEKK1 upon ligation. TRAF2, Ubc13, and IKKgamma were required for complex assembly and activation of MEKK1 and MAPK cascades. However, these kinases were not activated unless the multicomponent signaling complex translocated from CD40 to the cytosol upon c-IAP1/2-induced degradation of TRAF3. This two-stage signaling mechanism may apply to other innate immune receptors, accounting for spatial and temporal separation of MAPK and IKK signaling.