线纹海马Hippocampus erectus的tlr21基因结构及其对CpG-ODN的应答特征
|
摘要
作为先天性免疫反应中重要的模式识别受体之一,TLR(toll-likereceptor)基因家族介导的先天性免疫是脊椎动物抵御病原微生物的重要防线。研究分析了线纹海马Hippocampus erectus tlr21基因的序列特征,并基于抗原注射实验探讨了海马tlr21的免疫功能。线纹海马tlr21基因的开放阅读框长度为2946bp,编码981个氨基酸,预测其编码蛋白相对分子量为246.98kDa,理论等电点为4.78。tlr21编码蛋白主要包含1个信号肽和3个功能结构域:胞外区具有14个富含亮氨酸重复序列的结构域(LRR),跨膜区具有富含半胱氨酸的结构域,胞内区则具有TIR结构域。同源性比较和系统进化分析表明,线纹海马tlr21基因与虎尾海马Hippocampuscomestlr21基因的同源性最高,其次与斜带石斑鱼Epinephelus coioides、牙鲆Paralichthys olivaceus、大菱鲆Scophthalmus maximus和红鳍东方鲀Takifugu rubripes的tlr21基因聚为一枝。tlr21基因在线纹海马的脑、鳃、肝、肠、肾、性腺、肌肉和育儿袋各组织均有分布,肾脏中表达量最高。抗原注射实验结果发现,线纹海马Tlr21对不同类型CpG寡脱氧核苷酸(CpG-ODNs)的识别能力存在差异,其中,CpG-2007和CpG-HC4040对海马肾脏tlr21的mRNA表达量具有显著的促进作用(P<0.05)。研究表明,线纹海马Tlr21能够通过识别含CpG序列的DNA发挥免疫识别作用,研究结果将有助于系统认识海马免疫系统中TLR家族基因的功能特征,为建立海马病害防治策略提供理论依据。
Toll-like receptors(TLRs) are the major pattern recognition receptors(PRR) of the innate immune system in vertebrates, which can initiate host immune responses by recognizing potential pathogens. The present study focused on the role of Tlr21 involved in immune responses in lined seahorse(Hippocampus erectus). The full-length sequence of the lined seahorse tlr21 gene was cloned. The open reading frame(ORF) of seahorse tlr21 gene includes 2964 base pairs, which is predicted to encode 981 amino acids. The encoding protein had a predicted molecular mass of 246.98 kDa and an estimated isoelectric point of 4.78. Homology comparison and phylogenetic analysis showed that lined seahorse tlr21 shared high sequence identity with its homologs from other species, especially those species in Syngnathidae. Quantitative real-time PCR analysis showed that tlr21 mRNA was widely expressed in various tissues and expressed highest in the kidney. We conducted intraperitoneal CpG-ODNs injections to the lined seahorses. Both CpG-2007 and CpG-HC4040 increased expression levels of tlr21 mRNA in seahorse kidney significantly. In conclusion, these findings indicated that tlr21 initiated the innate immunity in lined seahorse by recognizing CpG DNA.
Toll-like receptors(TLRs) are the major pattern recognition receptors(PRR) of the innate immune system in vertebrates, which can initiate host immune responses by recognizing potential pathogens. The present study focused on the role of Tlr21 involved in immune responses in lined seahorse(Hippocampus erectus). The full-length sequence of the lined seahorse tlr21 gene was cloned. The open reading frame(ORF) of seahorse tlr21 gene includes 2964 base pairs, which is predicted to encode 981 amino acids. The encoding protein had a predicted molecular mass of 246.98 kDa and an estimated isoelectric point of 4.78. Homology comparison and phylogenetic analysis showed that lined seahorse tlr21 shared high sequence identity with its homologs from other species, especially those species in Syngnathidae. Quantitative real-time PCR analysis showed that tlr21 mRNA was widely expressed in various tissues and expressed highest in the kidney. We conducted intraperitoneal CpG-ODNs injections to the lined seahorses. Both CpG-2007 and CpG-HC4040 increased expression levels of tlr21 mRNA in seahorse kidney significantly. In conclusion, these findings indicated that tlr21 initiated the innate immunity in lined seahorse by recognizing CpG DNA.
引文
李春艳,黄贝,熊静,等,2017.日本鳗鲡TLR21基因的鉴定、免疫应答与启动子分析[J].水生生物学报,41(2):296-305.LI CHUNYAN,HUANG BEI,XIONG JING,et al,2017.Molecular cloning and characterization of TLR21 gene from Japanese eel,Anguilla japonica[J].Acta Hydrobiologica Sinica,41(2):296-305(in Chinese with English abstract).
王凯伦,2017.黄颡鱼TLR18、TLR19和TLR21基因的克隆及表达分析[D].武汉:华中农业大学:31-35.WANG KAILUN,2017.Molecular cloning and expression analysis of the TLR18,TLR19 and TLR21 genes in yellow catfish(Pelteobagrus fulvidraco)[D].Wuhan:Huazhong Agricultural University:31-35(in Chinese with English abstract).
张洁,郑津辉,李庆亚,等,2015.牙鲆(Paralichthys olivaceus)TLR21基因在迟缓爱德华氏菌(Edwardsiella tarda)感染后的表达特征[J].海洋与湖沼,46(6):1502-1508.ZHANG JIE,ZHENG JINHUI,LI QINGYA,et al,2015.Expression of TLR21 gene in Paralichthys olivaceus challenged by Edwardsiella tarda[J].Oceanologia et Limnologia Sinica,46(6):1502-1508(in Chinese with English abstract).
BALLAS Z K,RASMUSSEN W L,KRIEG A M,1996.Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA[J].The Journal of Immunology,157(5):1840-1845.
BERNASCONI N L,ONAI N,LANZAVECCHIA A,2003.A role for Toll-like receptors in acquired immunity:up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells[J].Blood,101(11):4500-4504.
BROWNLIE R,ZHU JIANZHONG,ALLAN B,et al,2009.Chicken TLR21 acts as a functional homologue to mammalian TLR9 in the recognition of Cp G oligodeoxynucleotides[J].Molecular Immunology,46(15):3163-3170.
CARRINGTON A C,COLLET B,HOLLAND J W,et al,2004.Cp G oligodeoxynucleotides stimulate immune cell proliferation but not specific antibody production in rainbow trout(Oncorhynchus mykiss)[J].Veterinary Immunology and Immunopathology,101(3-4):211-222.
CHAUNG H C,2006.Cp G oligodeoxynucleotides as DNAadjuvants in vertebrates and their applications in immunotherapy[J].International Immunopharmacology,6(10):1586-1596.
COOPER C L,AHLUWALIA N K,EFLER S M,et al,2008.Immunostimulatory effects of three classes of Cp Goligodeoxynucleotides on PBMC from HCV chronic carriers[J].Journal of Immune Based Therapies and Vaccines,6:3.
GüRSEL M,VERTHELYI D,GüRSEL I,et al,2002.Differential and competitive activation of human immune cells by distinct classes of CpG oligodeoxynucleotide[J].Journal of Leukocyte Biology,71(5):813-820.
GAO HONG,WU LIAN,SUN JINSHENG,et al,2013.Molecular characterization and expression analysis of Toll-like receptor21 c DNA from Paralichthys olivaceu[J].Fish&Shellfish Immunology,35(4):1138-1145.
HARTMANN G,BATTIANY J,POECK H,et al,2003.Rational design of new Cp G oligonucleotides that combine B cell activation with high IFN-αinduction in plasmacytoid dendritic cells[J].European Journal of Immunology,33(6):1633-1641.
HEMMI H,TAKEUCHI O,KAWAI T,et al,2000.A Toll-like receptor recognizes bacterial DNA[J].Nature,408(6813):740-745.
HWANG S D,KONDO H,HIRONO I,et al,2011.Molecular cloning and characterization of Toll-like receptor 14 in Japanese flounder,Paralichthys olivaceus[J].Fish&Shellfish Immunology,30(1):425-429.
ISHII A,KAWASAKI M,MATSUMOTO M,et al,2007.Phylogenetic and expression analysis of amphibian Xenopus Toll-like receptors[J].Immunogenetics,59(4):281-293.
JANEWAY C A JR,MEDZHITOV R,2012.Innate immune recognition[J].Annual Review of Immunology,2002,20(1):197-216.
J?RGENSEN J B,JOHANSER L H,STEIRO K,et al,2003.Cp G-DNA induces protective antiviral immune responses in Atlantic salmon(Salmo salar L.)[J].Journal of Virology,77(21):11471-11479.
KANG J Y,LEE J O,2011.Structural biology of the Toll-like receptor family[J].Annual Review of Biochemistry,80:917-941.
KAWAI T,AKIRA S,2010.The role of pattern-recognition receptors in innate immunity:update on Toll-like receptors[J].Nature Immunology,11(5):373-384.
KEESTRA A M,DE ZOETE M R,BOUWMAN L I,et al,2010.Chicken TLR21 is an innate CpG DNA receptor distinct from mammalian TLR9[J].Journal of Immunology,185(1):460-467.
KRIEG A M,2002.CpG motifs in bacterial DNA and their immune effects[J].Annual Review of Immunology,20:709-760.
KRIEG A M,YI A K,MATSON S,et al,1995.CpG motifs in bacterial DNA trigger direct B-cell activation[J].Nature,374(6522):546-549.
KRUG A,ROTHENFUSSER S,HORNUNG V,et al,2001.Identification of Cp G oligonucleotide sequences with high induction of IFN-α/βin plasmacytoid dendritic cells[J].European Journal of Immunology,31(7):2154-2163.
LI SONG,WANG GUANJIE,LIU DAHAI,et al,2017.Cloning and expression analysis of a Toll-like receptor 21(TLR21)gene from turbot,Scophthalmus maximus[J].Developmental&Comparative Immunology,73:163-168.
LI YANWEI,LUO XIAOCHUN,DAN XUEMING,et al,2012.Molecular cloning of orange-spotted grouper(Epinephelus coioides)TLR21 and expression analysis post Cryptocaryon irritans infection[J].Fish&Shellfish Immunology,32(3):476-481.
LIN QIANG,FAN SHAOHUA,ZHANG YANHONG,et al,2016.The seahorse genome and the evolution of its specialized morphology[J].Nature,540(7633):395-399.
LIVAK K J,SCHMITTGEN T D,2001.Analysis of relative gene expression data using real-time quantitative PCR and the2-ΔΔCT method[J].Methods,25(4):402-408.
MARSHALL J D,FEARON K C,ABBATE C,et al,2003.Identification of a novel Cp G DNA class and motif that optimally stimulate B cell and plasmacytoid dendritic cell functions[J].Journal of Leukocyte Biology,73(6):781-792.
MATSUNAGA T,RAHMAN A,1998.What brought the adaptive immune system to vertebrates?--The jaw hypothesis and the seahorse[J].Immunological Reviews,166(1):177-186.
MEIJER A H,KRENS S F G,RODRIGUEZ I A M,et al,2004.Expression analysis of the Toll-like receptor and TIR domain adaptor families of zebrafish[J].Molecular Immunology,40(11):773-783.
MORESCO E M Y,LAVINE D,BEUTLER B,2011.Toll-like receptors[J].Current Biology,21(13):R488-R493.
O’NEILL L A,GOLENBOCK D,BOWIE A G,2013.The history of Toll-like receptors-redefining innate immunity[J].Nature Reviews Immunology,13(6):453-460.
O’NEILL L,FITZGERALD K A,BOWIE A G,2003.The Toll-IL-1 receptor adaptor family grows to five members[J].Trends in Immunology,24(6):286-289.
OSHIUMI H,TSUJITA T,SHIDA K,et al,2003.Prediction of the prototype of the human Toll-like receptor gene family from the pufferfish,Fugu rubripes,genome[J].Immunogenetics,54(11):791-800.
PALTI Y,2011.Toll-like receptors in bony fish:from genomics to function[J].Developmental&Comparative Immunology,35(12):1263-1272.
QUINIOU S M A,BOUDINOT P,BENGTéN E,2013.Comprehensive survey and genomic characterization of Toll-like receptors(TLRs)in channel catfish,Ictalurus punctatus:identification of novel fish TLRs[J].Immunogenetics,65(7):511-530.
REYES-BECERRIL M,ASCENCIO-VALLE F,HIRONO I,et al,2016.TLR21's agonists in combination with Aeromonas antigens synergistically up-regulate functional TLR21 and cytokine gene expression in yellowtail leucocytes[J].Developmental&Comparative Immunology,61:107-115.
SATO Y,ROMAN M,TIGHE H,et al,1996.Immunostimulatory DNA sequences necessary for effective intradermal gene immunization[J].Science,273(5273):352-354.
SLACK J L,SCHOOLEY K,BONNERT T P,et al,2000.Identification of two major sites in the type I interleukin-1receptor cytoplasmic region responsible for coupling to pro-inflammatory signaling pathways[J].Journal of Biological Chemistry,275(7):4670-4678.
SUNDARAM A Y M,KIRON V,DOPAZO J,et al,2012.Diversification of the expanded teleost-specific toll-like receptor family in Atlantic cod,Gadus morhua[J].BMCEvolutionary Biology,12(1):256.
TAKANO T,DON HWANG S,KONDO H,et al,2010.Evidence of molecular toll-like receptor mechanisms in teleosts[J].Fish Pathology,45(1):1-16.
TAKEDA K,KAISHO T,AKIRA S,2003.Toll-like receptors[J].Annual Review of Immunology,21(1):335-376.
TASSAKKA A C M A R,SAKAI M,2003.The in vitro effect of Cp G-ODNs on the innate immune response of common carp,Cyprinus carpio L.[J].Aquaculture,220(1-4):27-36.
TEMPERLY N D,BERLIN S,PATON I R,et al,2008.Evolution of the chicken Toll-like receptor gene family:A story of gene gain and gene loss[J].BMC Genomics,9(1):62.
VALENZUELA C A,ZULOAGA R,POBLETEM-MOTALES M,et al,2017.Fish skeletal muscle tissue is an important focus of immune reactions during pathogen infection[J].Developmental&Comparative Immunology,73:1-9.
VOLLMER J,WEERATNA R,PAYETTE P,et al,2004.Characterization of three Cp G oligodeoxynucleotide classes with distinct immunostimulatory activities[J].European Journal of Immunology,34(1):251-262.
WANG JINLAN,ZHANG ZHENG,LIU JING,et al,2015.Structural characterization and evolutionary analysis of fish-specific TLR27[J].Fish&Shellfish Immunology,45(2):940-945.
WANG WENJING,SHEN YUBANG,PANDIT N P,et al,2013.Molecular cloning,characterization and immunological response analysis of Toll-like receptor 21(TLR21)gene in grass carp,Ctenopharyngodon idella[J].Developmental&Comparative Immunology,40(3-4):227-231.
YEH D W,LAI CHAOYANG,LIU YILING,et al,2017.Cp G-oligodeoxynucleotides developed for grouper toll-like receptor(TLR)21s effectively activate mouse and human TLR9s mediated immune responses[J].Scientific Reports,7(1):17297.
YEH DAWEI,LIU YILING,LO YINCHIU,et al,2013.Toll-like receptor 9 and 21 have different ligand recognition profiles and cooperatively mediate activity of CpG-oligodeoxynucleotides in zebrafish[J].Proceedings of the National Academy of Sciences of the United States of America,110(51):20711-20716.
王凯伦,2017.黄颡鱼TLR18、TLR19和TLR21基因的克隆及表达分析[D].武汉:华中农业大学:31-35.WANG KAILUN,2017.Molecular cloning and expression analysis of the TLR18,TLR19 and TLR21 genes in yellow catfish(Pelteobagrus fulvidraco)[D].Wuhan:Huazhong Agricultural University:31-35(in Chinese with English abstract).
张洁,郑津辉,李庆亚,等,2015.牙鲆(Paralichthys olivaceus)TLR21基因在迟缓爱德华氏菌(Edwardsiella tarda)感染后的表达特征[J].海洋与湖沼,46(6):1502-1508.ZHANG JIE,ZHENG JINHUI,LI QINGYA,et al,2015.Expression of TLR21 gene in Paralichthys olivaceus challenged by Edwardsiella tarda[J].Oceanologia et Limnologia Sinica,46(6):1502-1508(in Chinese with English abstract).
BALLAS Z K,RASMUSSEN W L,KRIEG A M,1996.Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA[J].The Journal of Immunology,157(5):1840-1845.
BERNASCONI N L,ONAI N,LANZAVECCHIA A,2003.A role for Toll-like receptors in acquired immunity:up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells[J].Blood,101(11):4500-4504.
BROWNLIE R,ZHU JIANZHONG,ALLAN B,et al,2009.Chicken TLR21 acts as a functional homologue to mammalian TLR9 in the recognition of Cp G oligodeoxynucleotides[J].Molecular Immunology,46(15):3163-3170.
CARRINGTON A C,COLLET B,HOLLAND J W,et al,2004.Cp G oligodeoxynucleotides stimulate immune cell proliferation but not specific antibody production in rainbow trout(Oncorhynchus mykiss)[J].Veterinary Immunology and Immunopathology,101(3-4):211-222.
CHAUNG H C,2006.Cp G oligodeoxynucleotides as DNAadjuvants in vertebrates and their applications in immunotherapy[J].International Immunopharmacology,6(10):1586-1596.
COOPER C L,AHLUWALIA N K,EFLER S M,et al,2008.Immunostimulatory effects of three classes of Cp Goligodeoxynucleotides on PBMC from HCV chronic carriers[J].Journal of Immune Based Therapies and Vaccines,6:3.
GüRSEL M,VERTHELYI D,GüRSEL I,et al,2002.Differential and competitive activation of human immune cells by distinct classes of CpG oligodeoxynucleotide[J].Journal of Leukocyte Biology,71(5):813-820.
GAO HONG,WU LIAN,SUN JINSHENG,et al,2013.Molecular characterization and expression analysis of Toll-like receptor21 c DNA from Paralichthys olivaceu[J].Fish&Shellfish Immunology,35(4):1138-1145.
HARTMANN G,BATTIANY J,POECK H,et al,2003.Rational design of new Cp G oligonucleotides that combine B cell activation with high IFN-αinduction in plasmacytoid dendritic cells[J].European Journal of Immunology,33(6):1633-1641.
HEMMI H,TAKEUCHI O,KAWAI T,et al,2000.A Toll-like receptor recognizes bacterial DNA[J].Nature,408(6813):740-745.
HWANG S D,KONDO H,HIRONO I,et al,2011.Molecular cloning and characterization of Toll-like receptor 14 in Japanese flounder,Paralichthys olivaceus[J].Fish&Shellfish Immunology,30(1):425-429.
ISHII A,KAWASAKI M,MATSUMOTO M,et al,2007.Phylogenetic and expression analysis of amphibian Xenopus Toll-like receptors[J].Immunogenetics,59(4):281-293.
JANEWAY C A JR,MEDZHITOV R,2012.Innate immune recognition[J].Annual Review of Immunology,2002,20(1):197-216.
J?RGENSEN J B,JOHANSER L H,STEIRO K,et al,2003.Cp G-DNA induces protective antiviral immune responses in Atlantic salmon(Salmo salar L.)[J].Journal of Virology,77(21):11471-11479.
KANG J Y,LEE J O,2011.Structural biology of the Toll-like receptor family[J].Annual Review of Biochemistry,80:917-941.
KAWAI T,AKIRA S,2010.The role of pattern-recognition receptors in innate immunity:update on Toll-like receptors[J].Nature Immunology,11(5):373-384.
KEESTRA A M,DE ZOETE M R,BOUWMAN L I,et al,2010.Chicken TLR21 is an innate CpG DNA receptor distinct from mammalian TLR9[J].Journal of Immunology,185(1):460-467.
KRIEG A M,2002.CpG motifs in bacterial DNA and their immune effects[J].Annual Review of Immunology,20:709-760.
KRIEG A M,YI A K,MATSON S,et al,1995.CpG motifs in bacterial DNA trigger direct B-cell activation[J].Nature,374(6522):546-549.
KRUG A,ROTHENFUSSER S,HORNUNG V,et al,2001.Identification of Cp G oligonucleotide sequences with high induction of IFN-α/βin plasmacytoid dendritic cells[J].European Journal of Immunology,31(7):2154-2163.
LI SONG,WANG GUANJIE,LIU DAHAI,et al,2017.Cloning and expression analysis of a Toll-like receptor 21(TLR21)gene from turbot,Scophthalmus maximus[J].Developmental&Comparative Immunology,73:163-168.
LI YANWEI,LUO XIAOCHUN,DAN XUEMING,et al,2012.Molecular cloning of orange-spotted grouper(Epinephelus coioides)TLR21 and expression analysis post Cryptocaryon irritans infection[J].Fish&Shellfish Immunology,32(3):476-481.
LIN QIANG,FAN SHAOHUA,ZHANG YANHONG,et al,2016.The seahorse genome and the evolution of its specialized morphology[J].Nature,540(7633):395-399.
LIVAK K J,SCHMITTGEN T D,2001.Analysis of relative gene expression data using real-time quantitative PCR and the2-ΔΔCT method[J].Methods,25(4):402-408.
MARSHALL J D,FEARON K C,ABBATE C,et al,2003.Identification of a novel Cp G DNA class and motif that optimally stimulate B cell and plasmacytoid dendritic cell functions[J].Journal of Leukocyte Biology,73(6):781-792.
MATSUNAGA T,RAHMAN A,1998.What brought the adaptive immune system to vertebrates?--The jaw hypothesis and the seahorse[J].Immunological Reviews,166(1):177-186.
MEIJER A H,KRENS S F G,RODRIGUEZ I A M,et al,2004.Expression analysis of the Toll-like receptor and TIR domain adaptor families of zebrafish[J].Molecular Immunology,40(11):773-783.
MORESCO E M Y,LAVINE D,BEUTLER B,2011.Toll-like receptors[J].Current Biology,21(13):R488-R493.
O’NEILL L A,GOLENBOCK D,BOWIE A G,2013.The history of Toll-like receptors-redefining innate immunity[J].Nature Reviews Immunology,13(6):453-460.
O’NEILL L,FITZGERALD K A,BOWIE A G,2003.The Toll-IL-1 receptor adaptor family grows to five members[J].Trends in Immunology,24(6):286-289.
OSHIUMI H,TSUJITA T,SHIDA K,et al,2003.Prediction of the prototype of the human Toll-like receptor gene family from the pufferfish,Fugu rubripes,genome[J].Immunogenetics,54(11):791-800.
PALTI Y,2011.Toll-like receptors in bony fish:from genomics to function[J].Developmental&Comparative Immunology,35(12):1263-1272.
QUINIOU S M A,BOUDINOT P,BENGTéN E,2013.Comprehensive survey and genomic characterization of Toll-like receptors(TLRs)in channel catfish,Ictalurus punctatus:identification of novel fish TLRs[J].Immunogenetics,65(7):511-530.
REYES-BECERRIL M,ASCENCIO-VALLE F,HIRONO I,et al,2016.TLR21's agonists in combination with Aeromonas antigens synergistically up-regulate functional TLR21 and cytokine gene expression in yellowtail leucocytes[J].Developmental&Comparative Immunology,61:107-115.
SATO Y,ROMAN M,TIGHE H,et al,1996.Immunostimulatory DNA sequences necessary for effective intradermal gene immunization[J].Science,273(5273):352-354.
SLACK J L,SCHOOLEY K,BONNERT T P,et al,2000.Identification of two major sites in the type I interleukin-1receptor cytoplasmic region responsible for coupling to pro-inflammatory signaling pathways[J].Journal of Biological Chemistry,275(7):4670-4678.
SUNDARAM A Y M,KIRON V,DOPAZO J,et al,2012.Diversification of the expanded teleost-specific toll-like receptor family in Atlantic cod,Gadus morhua[J].BMCEvolutionary Biology,12(1):256.
TAKANO T,DON HWANG S,KONDO H,et al,2010.Evidence of molecular toll-like receptor mechanisms in teleosts[J].Fish Pathology,45(1):1-16.
TAKEDA K,KAISHO T,AKIRA S,2003.Toll-like receptors[J].Annual Review of Immunology,21(1):335-376.
TASSAKKA A C M A R,SAKAI M,2003.The in vitro effect of Cp G-ODNs on the innate immune response of common carp,Cyprinus carpio L.[J].Aquaculture,220(1-4):27-36.
TEMPERLY N D,BERLIN S,PATON I R,et al,2008.Evolution of the chicken Toll-like receptor gene family:A story of gene gain and gene loss[J].BMC Genomics,9(1):62.
VALENZUELA C A,ZULOAGA R,POBLETEM-MOTALES M,et al,2017.Fish skeletal muscle tissue is an important focus of immune reactions during pathogen infection[J].Developmental&Comparative Immunology,73:1-9.
VOLLMER J,WEERATNA R,PAYETTE P,et al,2004.Characterization of three Cp G oligodeoxynucleotide classes with distinct immunostimulatory activities[J].European Journal of Immunology,34(1):251-262.
WANG JINLAN,ZHANG ZHENG,LIU JING,et al,2015.Structural characterization and evolutionary analysis of fish-specific TLR27[J].Fish&Shellfish Immunology,45(2):940-945.
WANG WENJING,SHEN YUBANG,PANDIT N P,et al,2013.Molecular cloning,characterization and immunological response analysis of Toll-like receptor 21(TLR21)gene in grass carp,Ctenopharyngodon idella[J].Developmental&Comparative Immunology,40(3-4):227-231.
YEH D W,LAI CHAOYANG,LIU YILING,et al,2017.Cp G-oligodeoxynucleotides developed for grouper toll-like receptor(TLR)21s effectively activate mouse and human TLR9s mediated immune responses[J].Scientific Reports,7(1):17297.
YEH DAWEI,LIU YILING,LO YINCHIU,et al,2013.Toll-like receptor 9 and 21 have different ligand recognition profiles and cooperatively mediate activity of CpG-oligodeoxynucleotides in zebrafish[J].Proceedings of the National Academy of Sciences of the United States of America,110(51):20711-20716.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |