Retinoic acid-inducible gene I(RIG-l)-like receptors(RLRs)are RNA sensor molecules that play essential roles in innate antiviral immunity.Among the three RLRs encoded by the human genome,RIG-1 and melanoma differentia...Retinoic acid-inducible gene I(RIG-l)-like receptors(RLRs)are RNA sensor molecules that play essential roles in innate antiviral immunity.Among the three RLRs encoded by the human genome,RIG-1 and melanoma differentiation-associated gene 5,which contain N-terminal caspase recruitment domains,are activated upon the detection of viral RNAs in the cytoplasm of virus-infected cells.Activated RLRs induce downstream signaling via their interactions with mitochondrial antiviral signaling proteins and activate the production of type Ⅰ and Ⅲ interferons and inflammatory cytokines.Recent studies have shown that RLR-mediated signaling is regulated by interactions with endogenous RNAs and host proteins,such as those involved in stress responses and posttranslational modifications.Since RLR-mediated cytokine production is also involved in the regulation of acquired immunity,the deregulation of RLR-mediated signaling is associated with autoimmune and autoinflammatory disorders.Moreover,RLRmediated signaling might be involved in the aberrant cytokine production observed in coronavirus disease 2019.Since the discovery of RLRs in 2004,significant progress has been made in understanding the mechanisms underlying the activation and regulation of RLR-mediated signaling pathways.Here,we review the recent advances in the understanding of regulated RNA recognition and signal activation by RLRs,focusing on the interactions between various host and viral factors.展开更多
Pattern recognition receptors （PRRs） and their signaling pathways have essential roles in recognizing various components of pathogens as well as damaged cells and triggering inflammatory responses that eliminate inv...Pattern recognition receptors （PRRs） and their signaling pathways have essential roles in recognizing various components of pathogens as well as damaged cells and triggering inflammatory responses that eliminate invading microorganisms and damaged cells. The zebrafish relies heavily on these primary defense mechanisms against pathogens. Here, we review the major PRR signaling pathways in the zebrafish innate immune system and compare these signaling pathways in zebrafish and humans to reveal their evolutionary relationship and better understand their innate immune defense mechanisms.展开更多
Pattern recognition receptors(PRRs) play important roles in innate immunity system and trigger the specific pathogen recognition by detecting the pathogen-associated molecular patterns. The main four PRRs components i...Pattern recognition receptors(PRRs) play important roles in innate immunity system and trigger the specific pathogen recognition by detecting the pathogen-associated molecular patterns. The main four PRRs components including Toll-like receptors(TLRs), RIG-I-like receptors(RLRs), NOD-like receptors(NLRs) and C-type lectin receptors(CLRs) were surveyed in the five genomes of non-teleost ray-finned fishes(NTR) including bichir(Polypterus senegalus), American paddlefish(Polyodon spathula), alligator gar(Atractosteus spatula), spotted gar(Lepisosteus oculatus) and bowfin(Amia calva), representing all the four major basal groups of ray-finned fishes. The result indicates that all the four PRRs components have been well established in these NTR fishes. In the RLR-MAVS signal pathway, which detects intracellular RNA ligands to induce production of type I interferons(IFNs), the MAVS was lost in bichir particularly. Also, the essential genes of recognition of Lipopolysaccharide(LPS) commonly in mammals like MD2, LY96 and LBP could not be identified in NTR fishes. It is speculated that TLR4 in NTR fishes may act as a cooperator with other PRRs and has a different pathway of recognizing LPS compared with that in mammals. In addition, we provide a survey of NLR and CLR in NTR fishes. The CLRs results suggest that Group V receptors are absent in fishes and Group II and VI receptors are well established in the early vertebrate evolution. Our comprehensive research of PRRs involving NTR fishes provides a new insight into PRR evolution in primitive vertebrate.展开更多
Bacterial pathogens have evolved various mechanisms to modulate host immune responses for successful infection. In this study, RNA- sequencing technology was used to analyze the responses of human monocytes THP1 to Ye...Bacterial pathogens have evolved various mechanisms to modulate host immune responses for successful infection. In this study, RNA- sequencing technology was used to analyze the responses of human monocytes THP1 to Yersinia pestis infection. Over 6000 genes were differentially expressed over the 12 h infection. Kinetic responses of pathogen recognition receptor signaling pathways, apoptosis, antigen processing, and presentation pathway and coagulation system were analyzed in detail. Among them, RIG-I-like receptor （RLR） signaling pathway, which was established for antiviral defense, was significantly affected. Mice lacking MAVS, the adaptor of the RLR signaling pathway, were less sensitive to infection and exhibited lower IFN-13 production, higher Thl-type cytokines IFN-γ and IL-12 production, and lower Th2-type cytokines IL-4 and IL-13 production in the serum compared with wild-type mice. Moreover, infection of pathogenic bacteria other than E pestis also altered the expression of the RLR pathway, suggesting that the response of RLR pathway to bacterial infection is a universal mechanism.展开更多
机体如何识别以及清除入侵的病毒一直是免疫学研究的重点,然而对于病毒与宿主细胞相互作用的最早期信号事件的了解甚微。近几年的研究工作在先天性免疫系统如何识别早期病毒的入侵方面取得了重大进展。RIG-I样受体(RIG-I Like Receptors...机体如何识别以及清除入侵的病毒一直是免疫学研究的重点,然而对于病毒与宿主细胞相互作用的最早期信号事件的了解甚微。近几年的研究工作在先天性免疫系统如何识别早期病毒的入侵方面取得了重大进展。RIG-I样受体(RIG-I Like Receptors,RLRs)是一类新发现的胞浆内模式识别受体,能够识别细胞质中的病毒核酸,由3个成员组成,分别是RIG-I(Retinoic Acid-inducible Gene I)、MDA5(Melanoma Differentiation-Associated Gene5)和LGP2(Laboratory of Genetics and Physiology 2)。它们可通过自身的CARD结构域与下游信号分子线粒体连接蛋白(Mitochondrial Antiviral Signalling Protein,MAVS)的CARD结构域间的相互作用,激活细胞转录因子IRF和NF-κB,诱导干扰素和促炎症细胞因子的产生,从而启动固有免疫应答和调节随后的获得性免疫应答,增强机体抵抗病毒的能力。因此,RLRs对抗病毒天然免疫的建立起着非常重要的作用。文章将分别就RLRs的组成结构、对病毒核酸等靶分子的识别及其相关信号传导途径方面所取得的主要研究进展做一概述,以期为海洋生物(特别是硬骨鱼类)的抗病毒免疫应答等相关研究提供参考。展开更多
非特异性固有免疫是预防病毒感染的第一道防线,Toll样受体(toll-like receptors,TLRs)和维甲酸诱导基因I样受体(RIG-I like receptors,RLRs)是感知病毒RNA的两个主要受体家族。RLRs为存在于胞浆中的RNA解旋酶家族,可识别在病毒感染或复...非特异性固有免疫是预防病毒感染的第一道防线,Toll样受体(toll-like receptors,TLRs)和维甲酸诱导基因I样受体(RIG-I like receptors,RLRs)是感知病毒RNA的两个主要受体家族。RLRs为存在于胞浆中的RNA解旋酶家族,可识别在病毒感染或复制期间进入到胞浆内的单链或双链RNA。目前研究RLRs家族比较多的成员有维甲酸诱导型基因I(retinoic acid-inducible gene I,RIG-I)、黑色素瘤分化相关基因5(melanoma differentiation associated gene-5,MDA-5)及遗传学和生理学实验室蛋白2(laboratory of genetics and physiology 2,LGP2)。本文分别就RLRs家族中RIG-I和MDA-5结构、生物学作用及其信号传导中关键分子的研究进展作一概述。展开更多
基金supported by Grants-in-Aids for Scientific Research(B)(18H02660)and(Q(19K07589 and 20K07534)from the Ministry of Education,Culture,Sports,Science,and Technology of Japan。
文摘Retinoic acid-inducible gene I(RIG-l)-like receptors(RLRs)are RNA sensor molecules that play essential roles in innate antiviral immunity.Among the three RLRs encoded by the human genome,RIG-1 and melanoma differentiation-associated gene 5,which contain N-terminal caspase recruitment domains,are activated upon the detection of viral RNAs in the cytoplasm of virus-infected cells.Activated RLRs induce downstream signaling via their interactions with mitochondrial antiviral signaling proteins and activate the production of type Ⅰ and Ⅲ interferons and inflammatory cytokines.Recent studies have shown that RLR-mediated signaling is regulated by interactions with endogenous RNAs and host proteins,such as those involved in stress responses and posttranslational modifications.Since RLR-mediated cytokine production is also involved in the regulation of acquired immunity,the deregulation of RLR-mediated signaling is associated with autoimmune and autoinflammatory disorders.Moreover,RLRmediated signaling might be involved in the aberrant cytokine production observed in coronavirus disease 2019.Since the discovery of RLRs in 2004,significant progress has been made in understanding the mechanisms underlying the activation and regulation of RLR-mediated signaling pathways.Here,we review the recent advances in the understanding of regulated RNA recognition and signal activation by RLRs,focusing on the interactions between various host and viral factors.
基金ACKNOWLEDGEMENTS TJ is supported by the Fundamental Research Funds for the Central Universities and the 100 Talents Program of the Chinese Academy of Sciences. YIL is supported by the China Postdoctoral Science Foundation. We express our appreciation to Tsan Sam Xiao at Case Western Reserve University and Bin Lin at the National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA for proofreading and suggestions.
文摘Pattern recognition receptors （PRRs） and their signaling pathways have essential roles in recognizing various components of pathogens as well as damaged cells and triggering inflammatory responses that eliminate invading microorganisms and damaged cells. The zebrafish relies heavily on these primary defense mechanisms against pathogens. Here, we review the major PRR signaling pathways in the zebrafish innate immune system and compare these signaling pathways in zebrafish and humans to reveal their evolutionary relationship and better understand their innate immune defense mechanisms.
基金supported by the National Natural Science Foundation of China(31372190)
文摘Pattern recognition receptors(PRRs) play important roles in innate immunity system and trigger the specific pathogen recognition by detecting the pathogen-associated molecular patterns. The main four PRRs components including Toll-like receptors(TLRs), RIG-I-like receptors(RLRs), NOD-like receptors(NLRs) and C-type lectin receptors(CLRs) were surveyed in the five genomes of non-teleost ray-finned fishes(NTR) including bichir(Polypterus senegalus), American paddlefish(Polyodon spathula), alligator gar(Atractosteus spatula), spotted gar(Lepisosteus oculatus) and bowfin(Amia calva), representing all the four major basal groups of ray-finned fishes. The result indicates that all the four PRRs components have been well established in these NTR fishes. In the RLR-MAVS signal pathway, which detects intracellular RNA ligands to induce production of type I interferons(IFNs), the MAVS was lost in bichir particularly. Also, the essential genes of recognition of Lipopolysaccharide(LPS) commonly in mammals like MD2, LY96 and LBP could not be identified in NTR fishes. It is speculated that TLR4 in NTR fishes may act as a cooperator with other PRRs and has a different pathway of recognizing LPS compared with that in mammals. In addition, we provide a survey of NLR and CLR in NTR fishes. The CLRs results suggest that Group V receptors are absent in fishes and Group II and VI receptors are well established in the early vertebrate evolution. Our comprehensive research of PRRs involving NTR fishes provides a new insight into PRR evolution in primitive vertebrate.
基金supported by the National Basic Research Program of China(Nos.2012CB518704 and 2013CB910804)the National Natural Science Foundation of China(No.31170122)the Basic Research Programs of Science and Technology Department Foundation of QingHai Province(No.2013-Z-748)
文摘Bacterial pathogens have evolved various mechanisms to modulate host immune responses for successful infection. In this study, RNA- sequencing technology was used to analyze the responses of human monocytes THP1 to Yersinia pestis infection. Over 6000 genes were differentially expressed over the 12 h infection. Kinetic responses of pathogen recognition receptor signaling pathways, apoptosis, antigen processing, and presentation pathway and coagulation system were analyzed in detail. Among them, RIG-I-like receptor （RLR） signaling pathway, which was established for antiviral defense, was significantly affected. Mice lacking MAVS, the adaptor of the RLR signaling pathway, were less sensitive to infection and exhibited lower IFN-13 production, higher Thl-type cytokines IFN-γ and IL-12 production, and lower Th2-type cytokines IL-4 and IL-13 production in the serum compared with wild-type mice. Moreover, infection of pathogenic bacteria other than E pestis also altered the expression of the RLR pathway, suggesting that the response of RLR pathway to bacterial infection is a universal mechanism.
文摘非特异性固有免疫是预防病毒感染的第一道防线,Toll样受体(toll-like receptors,TLRs)和维甲酸诱导基因I样受体(RIG-I like receptors,RLRs)是感知病毒RNA的两个主要受体家族。RLRs为存在于胞浆中的RNA解旋酶家族,可识别在病毒感染或复制期间进入到胞浆内的单链或双链RNA。目前研究RLRs家族比较多的成员有维甲酸诱导型基因I(retinoic acid-inducible gene I,RIG-I)、黑色素瘤分化相关基因5(melanoma differentiation associated gene-5,MDA-5)及遗传学和生理学实验室蛋白2(laboratory of genetics and physiology 2,LGP2)。本文分别就RLRs家族中RIG-I和MDA-5结构、生物学作用及其信号传导中关键分子的研究进展作一概述。
