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1.
模式识别受体(pattern-recognition receptors,PRRs)中的RIG-I样受体(RIG-I like receptors,RLRs)是细胞质中一类RNA解旋酶,它们可以通过其RNA配体结合病原相关分子模式(pathogen associated molecular pattern,PAMP),识别非自身的病毒RNA。被感染的细胞中,这种相互作用可以通过触发RLRs以及下游信号分子的活化,最终导致I型干扰素的产生和炎性因子的产生,细胞做出抗病毒免疫应答。本文简单介绍了RLR信号通路的组成及其泛素化调控,总结了病毒逃避RLR通路信号转导的机制,最后阐述了NOD样受体(NOD-like receptors,NLRs)通路对RLR通路的影响。通过对RLR信号通路分子在抗病毒免疫调节中的作用了解,可以为控制病毒的感染和免疫调节提供一个新的思路。 相似文献
2.
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. 相似文献
3.
《中国动物传染病学报》2018,(5)
天然免疫系统在识别病原和激发获得性免疫保护中发挥着重要作用,通过多种模式识别受体(pattern recognition receptors,PRRs)识别病原相关的分子模式(pathogen associated molecular patterns, PAMPs)抵御外来病原微生物的入侵。目前已知的天然免疫受体主要包括Toll样受体(toll-like receptors,TLRs)、视黄酸诱导基因-Ⅰ样解旋酶受体(retinoid acid-inducible gene-Ⅰ(RIG-Ⅰ)-likereceptors,RLRs)、核苷酸结合寡聚化结构域样受体(nucleotidebindingoligomerizationdomain(NOD)-likereceptors,NLRs)、C型凝集素样受体(C-typelectinreceptors,CLRs)以及DNA识别受体。其中,释放到胞内的病原核酸(RNA和DNA)作为一种重要的病原相关分子模式能被多种天然免疫受体识别。参与识别DNA的受体主要包括TLR9、γ干扰素诱导蛋白16(γ-interferon-inducible protein 16,IFI16)、DNA依赖的干扰素调节因子激活物(DNA-dependent activator of interferon-regulatory factors,DAI)、黑色素瘤缺乏因子2(absent in melanoma 2,AIM2),及最近发现的环鸟苷一腺苷酸合成酶(cyclic guanosine monophosphate-adenosine monophosphate synthase,cGAS)等,这些受体能激活I型干扰素途径早已被人熟知。近年来随着对DNA受体研究的进一步深入,人们对其参与机体抗病毒应答分子机制的认识更为深刻。本文主要对DNA识别受体的种类、DNA诱导的信号通路类型、cGAS-STING信号通路的调节机制、受体间的互作及对疾病的防御策略进行探讨。 相似文献
4.
《中国家禽》2020,(5)
模式识别受体在抗病毒天然免疫中发挥重要作用。这些受体识别微生物的保守结构并引发细胞内一系列级联反应,产生抗病毒效应。Toll样受体和RIG-I样受体是识别RNA的两大主要受体家族,其中能够识别病毒双链RNA(dsRNA)的RIG-I样家族在抗病毒免疫方面发挥关键作用。RIG-I样家族(RLR)的主要成员是RIG-I和MDA5,已有大量研究表明其能够引发相同的天然免疫信号,本文从多个角度阐述了两者的相似点和不同点,包括两者结构与定位、下游信号通路、抗病毒免疫、病毒对RLR信号的调节和逃逸,以及在禽类方面的研究进展。通过对RIG-I与MDA5多方面异同点的了解,能够对这些受体蛋白质以及家禽相关天然免疫有更深层次的认识,为免疫调节并控制病毒感染提供新思路。 相似文献
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天然免疫系统在病毒感染早期识别和诱发抗病毒反应中发挥重要作用,宿主模式识别受体(PRRs,如RIG-I、Toll和NOD样等受体)识别病原微生物结构上保守组分病原相关分子模式(PAMPs),进而激活下游级联信号通路,诱导干扰素、细胞因子和促炎性因子等产生,激发抗病毒天然免疫。而病毒通过降解天然免疫信号通路分子或抑制其激活,从而抑制抗病毒应答。口蹄疫病毒(FMDV)通过多种蛋白抑制天然免疫,肖少波团队和杜以军团队鉴定了非结构蛋白Lpro和3Cpro,作为水解酶蛋白,抑制RIG-I通路分子的激活,并阐明其抑制天然免疫的机制;郑海学团队鉴定了结构蛋白VP3和非结构蛋白2B和3A等抑制干扰素产生。 相似文献
7.
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. 相似文献
8.
Toll样受体(Toll-like receptors,TLR)是一类胚系编码的模式识别受体(Pattern recognition receptors,PRR),通过识别病原微生物保守的分子相关模式(Pathogen-associated molecular patterns,PAMP) 相似文献
9.
在病毒侵染机体的过程中,机体的多数组织器官可以高效产生干扰素。近些年的研究发现,能够有效识别病毒侵染机体过程中的相关模式分子(例如病毒复制中间产物双链RNA)的细胞受体是产生干扰素的主要感受器,这些细胞受体(例如Toll样受体和RIG-Ⅰ样受体)能够诱发一系列的信号级联反应,并且被激活的感受器可以启动干扰素相关基因的转录活性,从而产生特定的干扰素。值得注意的是,不同种类的病毒能够倾向性地去激活特定的细胞感受器,并且产生特定的信号转导通路。论文主要从Toll样受体和RIG-Ⅰ样受体的结构入手,讨论宿主细胞模式受体在干扰素抗病毒过程中行使的功能,并简单介绍干扰素在抗病毒过程中的信号级联反应。 相似文献
10.
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。 相似文献
11.
Toll样受体研究进展 总被引：4，自引：0，他引：4
免疫系统识别"非我"和"自我"的过程是依赖于不同的受体来完成的,作为先天性免疫系统的重要组成部分及连接获得性免疫与先天性免疫的"桥梁",Toll样受体(Toll-like receptors,TLRs)是生物的一种模式识别受体(pattern recognition receptor,PRR),它主要通过识别病原相关分子模式(pathogen-associated molecularpatterns,PAMPs)来启动免疫反应。已发现TLRs在炎症、细胞信号转导、细胞凋亡、肿瘤等发生过程中扮演重要角色。随着分子细胞生物学的发展,有关TLRs的研究必将更加深入,同时也会进一步拓展对机体免疫机制的认识。 相似文献
12.
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. 相似文献
13.
Microbes often infect the uterus and particularly the endometrium of animals. Infections are most commonly associated with natural service, pregnancy and the post-partum period, leading to inflammation with the elaboration of cytokines, chemokines and prostaglandins. Clinical diseases such as metritis, endometritis and abortion are important causes of infertility. The adaptive immune response to infection has been characterized previously, so the present review aims to highlight the emerging role for innate immunity in the endometrium. The detection of microbes and the innate immune response depends on the detection of pathogen-associated molecular patterns by pattern recognition receptors. The main families of pattern recognition receptors are Toll-like receptors (TLRs), nucleotide oligomerization domain-like receptors, retinoic acid-inducible gene I-like receptors and C-type lectin receptors. These receptors are most often expressed by hematopoietic cells, but the epithelial and stromal cells of the endometrium also possess functional receptors. For example, endometrial cells express TLR4 for recognition of the lipopolysaccharide endotoxin of Gram-negative bacteria, leading to secretion of IL-6, IL-8 and prostaglandin E(2) . It is likely that the epithelial and stromal cells provide a first line of defence in the endometrium to alert hematopoietic cells to the presence of microbes within the uterus. 相似文献
14.
TOLL-like receptors linking innate and adaptive immune response 总被引：25，自引：0，他引：25
Invading pathogens are controlled by the innate and adaptive arms of the immune system. Adaptive immunity, which is mediated by B and T lymphocytes, recognises pathogens by rearranged high affinity receptors. However, the establishment of adaptive immunity is often not rapid enough to eradicate microorganisms as it involves cell proliferation, gene activation and protein synthesis. More rapid defense mechanisms are provided by innate immunity, which recognises invading pathogens by germ-line-encoded pattern recognition receptors (PRR). Recent evidence shows that this recognition can mainly be attributed to the family of TOLL-like receptors (TLR). Binding of pathogen-associated molecular patterns (PAMP) to TLR induces the production of reactive oxygen and nitrogen intermediates (ROI and RNI), pro-inflammatory cytokines, and up-regulates expression of co-stimulatory molecules, subsequently initiating the adaptive immunity. In this review, we will summarize the discovery and the critical roles of the TLR family in host defense, briefly allude to signaling mechanisms mediating the response to TLR ligands, and will provide an update on current knowledge regarding the ligand specificity of these receptors and their role in immunity of domestic animals, particularly cattle. 相似文献
15.
Uenishi H Shinkai H Morozumi T Muneta Y 《Veterinary immunology and immunopathology》2012,148(1-2):69-73
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. 相似文献
16.
Toll样或非Toll样配体佐剂研究进展 总被引：1，自引：0，他引：1
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. 相似文献
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18.
Swerdlow MP Kennedy DR Kennedy JS Washabau RJ Henthorn PS Moore PF Carding SR Felsburg PJ 《Veterinary immunology and immunopathology》2006,114(3-4):313-319
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. 相似文献
19.
Toll样受体研究进展 总被引：2，自引：0，他引：2
Toll样受体(Toll-like receptors, TLRs)家族在病原体的识别和激活天然免疫方面发挥着非常重要的作用.激活TLRs不仅可以诱导天然免疫应答,而且有利于特异性免疫反应的发生,因而TLRs是天然免疫与获得性免疫之间的桥梁.不同TLRs可以有相同的功能,例如诱导炎性因子的产生或者上调辅助刺激分子的表达,也可以有特异的作用,例如具有诱导IFN-I产生的能力.这些作用不但在抗菌免疫反应中非常关键,而且也表现在自身免疫反应中.因而了解TLRs结构、分布、分类及功能可促进天然免疫机制研究的进一步深入,有利于对变态反应和自身免疫性疾病治疗措施的改进,也有利于解决诸如 CpG佐剂、DNA疫苗、预防过敏反应等实际应用过程中存在的问题. 相似文献