模式识别受体及其相关分子佐剂研究进展

综述了模式识别受体（Pattern recognition receptors,PRRs）及其相关分子佐剂的研究进展。PRRs是一类表达于固有免疫细胞并可识别病原体相关分子模式的识别分子。PRRs主要包括Toll样受体、NOD样受体、RIG—I样受体、清道夫受体、甘露糖受体和髓系细胞触发受体等。与PRRs直接相关的分子佐剂主要包括TLR激动剂、NLR激动剂、RIG—I和MDA5激动剂及CD40和肿瘤坏死因子受体超家族（TNFRSF）激动剂等。     

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。     

DNA识别受体在天然免疫反应中的作用

近年来,随着人们对哺乳动物模式识别受体(Pattern recognition receptors,PRRs)的发现和研究的不断深入,PRRs对病原,尤其是对病原生命物质基础--DNA和RNA的识别成为天然免疫学研究的热点和重点领域[1].PRRs主要包括Toll样受体(TLRs)家族、RIG-I样受体(RLRs)家族和蛋白激酶R(RNA-ativated protein kinase R,PKR、NOD样受体(NLRs)家族、C型凝集素受体(CLRs)家族、天然免疫特异性PRRs以及最近发现的DNA依赖的干扰素调节因子受体(DAI)家族、黑色素瘤缺乏因子2(AIM2)样受体(ALRs)家族和RNA聚合酶Ⅲ (RNA PolⅢ)等PRRs [2-3].这几类PRRs通过识别病原生存必不可少的特异性保守成分和机体应激或损伤时释放的结构成分,即病原/危险相关分子模式(PAMPs/DAMPs),诱导Ⅰ型干扰素(Ⅰ -IFNs)、炎性细胞因子、趋化因子和共刺激分子等的释放和表达发挥天然免疫防御功能,同时诱导获得性免疫的建立.     

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。     

Toll样受体与益生菌免疫

Toll样受体(Toll-like receptors,TLRs)是天然免疫反应中重要的细胞表面模式识别受体(pattern recognition receptors,PRRs),而益生菌在动物免疫中起着重要的作用,本文就TLRs的种类、配体类型和信号转导途径、益生菌的免疫作用、Toll样受体信号通路与益生菌的免疫作用的关系作简要综述。     

猪Toll样受体研究进展

Toll样受体(Toll-like receptors,TLRs)是哺乳动物重要的模式识别受体(Pattern-recognition receptors,PRRs),可广泛地识别病原相关分子模式(Pathogen associated molecular patterns,PAMPs)及自身配体分子,在机体抗感染免疫中发挥着重要作用。本文系统分析猪TLRs的种类、进化特点以及免疫相关的研究现状,发现猪TLRs广泛分布在各种组织细胞内,且在免疫相关组织或细胞上数量较多;猪与人的TLRs进化关系比较接近;不同TLRs在抵御病原入侵过程中发挥着相应的作用。对猪TLRs深入地认识将为今后猪病研究及人类某些疾病动物模型的建立提供理论参考。     

鸡Toll样受体的研究进展

Toll样受体(toll-like receptors,TLRs)是一类古老的序列高度保守的模式识别受体(pathogen-recognition receptors,PRRs),可选择性识别保守的     

TRIM蛋白参与天然免疫信号转导的研究进展

正天然免疫系统是宿主抵抗病原微生物感染的第一道防线。天然免疫对病原微生物最直接的杀灭和清除作用是通过天然免疫分子和吞噬细胞实现的~([1])。病原微生物所特有的能够被天然免疫细胞识别的靶分子称为病原相关分子模式(Pathogen associated molecular patterns,PAMPs),宿主细胞通过模式识别受体(Pattern recognition receptors,PRRs)     

NOD-1在介导固有免疫中的作用

机体对微生物入侵的免疫炎症应答过程中模式识别受体(pattern recognition receptors,PRRs)是启动机体天然免疫应答机制的关键,主要在获得性免疫系统被活化之前发挥抗感染作用。NODl作为一种新的胞内识别受体参与了细胞凋亡和核因子NF-KB的活化,并与一些炎症性疾病密切相关,在天然免疫中发挥了重要的作用。     

鸡传染性支气管炎病毒感染对雏鸡黏膜固有免疫相关受体和细胞因子转录水平的影响

为探讨鸡传染性支气管炎病毒(IBV)感染与宿主固有免疫系统的相互作用及其致病与免疫机制,本研究采用实时荧光定量RT-PCR方法检测IBV变异株GX-YL5感染鸡后不同时间点气管黏膜和哈德氏腺中固有免疫相关受体和细胞因子的mRNA水平以及IBV载量的动态变化。结果显示,气管黏膜和哈德氏腺中Toll样受体TLR2、TLR3、TLR6、TLR7、趋化因子MIP-1β和趋化因子受体CXCR4、CCR4在IBV感染后1~8天以及细胞因子IFN-α、IFN-β、IL-1β、IL-6、IL-10在IBV感染后1~5天,mRNA转录水平至少有一个时间点显著(P0.05)或极显著(P0.01)上调;感染后14~28天,一些受体和细胞因子的mRNA则出现下调;气管黏膜和哈德氏腺的IBV病毒载量在感染后立即上升,第3天达到峰值,随后下降。结果表明,IBV感染早期气管黏膜和哈德氏腺中固有免疫相关受体和细胞因子的mRNA转录水平显著上调,说明IBV感染对宿主固有免疫应答产生明显的影响。     

Pattern recognition receptors in equine endotoxaemia and sepsis

Pattern recognition receptors (PRRs) on host cells detect pathogens to activate innate immunity which, in turn, initiates inflammatory and adaptive immune responses. Successful activation of PRRs is, therefore, critical to controlling infections and driving pathogen-specific adaptive immunity, but overactivity of PRRs causes systemic inflammation, which is detrimental to the host. Here we review the PRR literature as it relates to horses and speculate on the role PRRs may play in sepsis and endotoxaemia.     

轮状病毒感染肠上皮细胞激活宿主先天免疫研究进展

轮状病毒(RV)是引起婴幼儿、幼畜禽急性肠胃炎的人畜共患病原,常与其他病原体混合感染,多以呕吐,严重水样腹泻,脱水为临床症状,感染后具有较高病死率,对人类公共卫生以及养殖业造成极大危害.RV病原相关分子模式(PAMP)可被肠上皮细胞(IECs)中一组可遗传的模式识别受体(PRR)识别,通过IECs、先天免疫细胞与RV互...     

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.     

Genomic survey of polymorphisms in pattern recognition receptors and their possible relationship to infections in pigs

Recent progress in the accumulation of pig genomic information has enabled us to comprehensively explore polymorphisms in pig genes. One of our targets for exploration has been the genes encoding molecules related to pathogen recognition, such as pattern recognition receptors (PRRs). PRRs play a role in the innate immune system, and possess various members such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-like helicases (RLHs), and C-type lectin-like receptors (CLRs). PRRs are required for the monitoring of pathogens; therefore, polymorphisms in PRRs may influence molecular functions such as ligand recognition. There have been many studies on the relationship between polymorphisms within PRR genes and disease susceptibility in humans and mice. Our studies have revealed that porcine PRR genes possess many nonsynonymous polymorphisms, particularly in regions encoding the ectodomains of TLRs localized on the cell surface. The genes encoding TLRs located on the membrane of intracellular compartments, and cytoplasmic PRRs such as NLRs and RLHs, also possessed nonsynonymous polymorphisms. Several observations indicate that there are relationships between polymorphisms in PRR or related genes and disease susceptibility in livestock animals including pig. Such information may contribute to breeding aimed at disease resistance, and effective vaccine design.     

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.     

The selective Dectin-1 agonist, curdlan, induces an oxidative burst response in chicken heterophils and peripheral blood mononuclear cells

A critical component of host innate immunity is recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). Dectin-1 is the primary PRR for exogenous beta-glucan, a component of fungal and bacterial cell walls. A previous study conducted in our laboratory demonstrated that administration of beta-glucan as a feed additive resulted in increased innate immune function of neonatal chickens, suggesting that chickens possess a Dectin-1-like beta-glucan receptor. In the present study, we demonstrated that heterophils and peripheral blood mononuclear cells (PBMCs) from day-old chicks had a significant increase in the generation of reactive oxygen species (ROS) following stimulation with the Dectin-1 specific agonist, curdlan. Pretreatment of heterophils and PBMCs with laminarin, a beta-glucan receptor blocking agent and specific inhibitor of Dectin-1 activity, significantly reduced the curdlan-induced ROS production. Together these data provide evidence for the first time of the presence of a functional Dectin-1-like beta-glucan receptor in chicken heterophils and PBMCs.     

Pattern recognition receptors in companion and farm animals - the key to unlocking the door to animal disease?

The innate immune system is essential for host defence and is responsible for early detection of potentially pathogenic microorganisms. Upon recognition of microbes by innate immune cells, such as macrophages and dendritic cells, diverse signalling pathways are activated that combine to define inflammatory responses that direct sterilisation of the threat and/or orchestrate development of the adaptive immune response. Innate immune signalling must be carefully controlled and regulation comes in part from interactions between activating and inhibiting signalling receptors. In recent years, an increasing number of pattern recognition receptors (PRRs), including C-type lectin receptors and Toll-like receptors (TLRs), has been described that participate in innate recognition of microbes, especially through the so called pathogen-associated molecular patterns (PAMPs). Recent studies demonstrate strong interactions between signalling through these receptors. Whereas useful models to study these receptors in great detail in the murine and human system are now emerging, relatively little is known regarding these receptors in companion and farm animals. In this review, current knowledge regarding these receptors in species of veterinary relevance is summarised.     

Development and characterization of a monoclonal antibody specific for bovine CD209

Dendritic cells (DC) play a central role in tailoring the immune response to pathogens. Effector activity is mediated through pattern recognition receptors (PRRs) that recognize pathogen associated molecular patterns (PAMPS). C-type lectin receptors (CLR) comprise a group of PRRs that recognize a broad range of pathogens. CD209 (DC-specific ICAM3-grabbing non-integrin, DC-SIGN) is a CLR expressed on DC that plays a critical role on DC function and pathogen recognition. It facilitates DC migration to peripheral tissues and local lymph nodes and mediates T cell activation by binding ICAM-2 (CD102) and ICAM-3 (CD50). The absence of monoclonal antibody (mAb) to bovine CD209 has limited the ability to characterize the phenotype and function of DC in cattle. To address this issue we developed and used a mAb to CD209 to characterize the phenotype of CD209 expressing cells in bovine blood using flow cytometry. Initial analysis has revealed the CD209 positive population in blood is comprised of multiple phenotypically defined subsets.     

To con protection: TIR-domain containing proteins (Tcp) and innate immune evasion

The innate immune system provides the host's first line of defence against invading pathogens. Key to the stimulation of the innate immune response is pattern-recognition receptors (PRRs), such as Toll-like receptors (TLRs), which recognize microbial-associated molecular patterns (MAMPs). Binding of MAMPs to TLRs triggers a signalling cascade resulting in the production of pro-inflammatory mediators. Central to this TLR signalling pathway are heterotypic protein–protein interactions mediated through Toll/interleukin-1 receptor (TIR) domains found in both the cytoplasmic regions of TLRs and several key adaptor proteins. Interestingly, TIR-domain containing proteins (Tcps) do not seem to be unique to the mammalian TLR system, but occurs in abundance in many biological forms. Recent evidence suggests that pathogenic bacteria have developed a range of ingenuous strategies to evade the host immune mechanisms involving Tcps. There is increasing evidence to suggest that these pathogen-encoded Tcps interfere directly with the TLR signalling pathway and thus inhibit the activation of NF-κB, with different modes of action and roles in virulence. Here, we review the current state of knowledge on the possible roles and mechanisms of action of bacterial encoded Tcp.