LIGHT在小鼠鹦鹉热衣原体呼吸道感染中的作用
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摘要
目的探讨LIGHT分子在鹦鹉热衣原体(Chlamydia psittaci,Cps)呼吸道感染过程中的作用。方法 C57BL/6J野生型(Wild type,WT)和LIGHT基因敲除(Knock out,KO)小鼠经鼻内接种4.5×10~5 IFU Cps,每天观察记录小鼠的进食、活动、体重变化及生存情况。感染后第4、9、14 d分批处死小鼠,分离肺组织,检测肺组织中Cps载量、病理损伤程度。结果与WT小鼠相比,LIGHT KO小鼠出现更严重的呼吸道感染症状,死亡率更高,肺组织匀浆中Cps载量更高且带菌时间延长,肺部病理损伤程度也显著高于WT小鼠。结论 LIGHT基因缺失可促进Cps呼吸道感染。
Objective To explore the role of lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells( LIGHT) costimulatory pathway in Chlamydia psittaci( Cps) respiratory tract infection. Methods Wild type(WT) and LIGHT knock out(KO) C57BL/6J mice were inoculated intranasally with 4.5×10~5 IFU Cps. The food intake,activities,body weight changes and survival rates were recorded every day.The mice were sacrificed on days 4,9 and 14 post-infection respectively,and then lung tissues were cllolected. Live Cps load and pathological changes in the lung were detected. Results LIGHT KO mice showed more serious respiratory tract symptoms and lower survival rate than WT mice. They developed much more severe pathological changes,and had higer Cps load and delayed Cps clearance in the lung homogenate. Conclusions The deficiency of LIGHT gene can aggravate Chlamydia psittaci respiratory tract infection.
Objective To explore the role of lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells( LIGHT) costimulatory pathway in Chlamydia psittaci( Cps) respiratory tract infection. Methods Wild type(WT) and LIGHT knock out(KO) C57BL/6J mice were inoculated intranasally with 4.5×10~5 IFU Cps. The food intake,activities,body weight changes and survival rates were recorded every day.The mice were sacrificed on days 4,9 and 14 post-infection respectively,and then lung tissues were cllolected. Live Cps load and pathological changes in the lung were detected. Results LIGHT KO mice showed more serious respiratory tract symptoms and lower survival rate than WT mice. They developed much more severe pathological changes,and had higer Cps load and delayed Cps clearance in the lung homogenate. Conclusions The deficiency of LIGHT gene can aggravate Chlamydia psittaci respiratory tract infection.
引文
[1]Stenzel T,Pestka D,Choszcz D.The prevalence and genetic characterization of Chlamydia psittaci from domestic and feral pigeons in Poland and the correlation between infection rate and incidence of pigeon circovirus[J].Poult Sci,2014,93(12):3009-3016.
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[4]Musicki K,Briscoe H,Britton WJ,et al.LIGHT contributes to early but not late control of Mycobacterium tuberculosis infection[J].Int Immunol,2010,22(5):353-358.
[5]Randall LM,Amante FH,Zhou Y,et al.Cutting edge:selective blockade of LIGHT-lymphotoxin beta receptor signaling protects mice from experimental cerebral malaria caused by Plasmodium berghei ANKA[J].J Immunol,2008,181(11):7458-7462.
[6]Stanley AC,de Labastida Rivera F,Haque A,et al.Critical roles for LIGHT and its receptors in generating T cell-mediated immunity during Leishmania donovani infection[J].PLo S Pathog,2011,7(10):e1002279.
[7]Harrop JA,Mc Donnell PC,Brigham-Burke M,et al.Herpesvirus entry mediator ligand(HVEM-L),a novel ligand for HVEM/TR2,stimulates proliferation of T cells and inhibits HT29 cell growth[J].J Biol Chem,1998,273(42):27548-27556.
[8]Harrop JA,Reddy M,Dede K,et al.Antibodies to TR2(herpesvirus entry mediator),a new member of the TNF receptor superfamily,block T cell proliferation,expression of activation markers,and production of cytokines[J].J Immunol,1998,161(4):1786-1794.
[9]Krause P,Zahner SP,Kim G,et al.The tumor necrosis factor family member TNFSF14(LIGHT)is required for resolution of intestinal inflammation in mice[J].Gastroenterology,2014,146(7):1752-1762.
[10]Xu G,Liu D,Okwor I,et al.LIGHT Is critical for IL-12 production by dendritic cells,optimal CD4+Th1 cell response,and resistance to Leishmania major[J].J Immunol,2007,179(10):6901-6909.
[11]Heo SK,Ju SA,Lee SC,et al.LIGHT enhances the bactericidal activity of human monocytes and neutrophils via HVEM[J].J Leukocyte Biol,2006,79(2):330-338.
[12]Wang J,Lo JC,Foster A,et al.The regulation of T cell homeostasis and autoimmunity by T cell-derived LIGHT[J].J Clin Invest,2001,108(12):1771-1780.
[13]陈丽丽,孙源彬,徐莎,等.LIGHT信号通路在鼠衣原体生殖道感染中的作用[J].微生物学报,2015,55(4):365-373.
[14]Dutow P,Fehlhaber B,Bode J,et al.The complement C3a receptor is critical in defense against Chlamydia psittaci in mouse lung infection and required for antibody and optimal T cell response[J].J Infect Dis,2014,209(8):1269-1278.
[15]Ehlers S,Holscher C,Scheu S,et al.The lymphotoxinβreceptor is critically involved in controlling infections with the intracellular pathogens Mycobacterium tuberculosis and Listeria monocytogenes[J].J Immunol,2003,170(10):5210-5218.
[2]Haag-Wackernagel D,Magnino S,Geigenfeind I.Chlamydial infections in feral pigeons in Europe:Review of data and focus on public health implications[J].Vet microbiol,2009,(1-2):54-67.
[3]Cheung TC.Modulation of T cell proliferation through the LIGHTHVEM-BTLA cosignaling pathway[J].Recent patents on DNA&gene sequences,2009,3(3):177-182.
[4]Musicki K,Briscoe H,Britton WJ,et al.LIGHT contributes to early but not late control of Mycobacterium tuberculosis infection[J].Int Immunol,2010,22(5):353-358.
[5]Randall LM,Amante FH,Zhou Y,et al.Cutting edge:selective blockade of LIGHT-lymphotoxin beta receptor signaling protects mice from experimental cerebral malaria caused by Plasmodium berghei ANKA[J].J Immunol,2008,181(11):7458-7462.
[6]Stanley AC,de Labastida Rivera F,Haque A,et al.Critical roles for LIGHT and its receptors in generating T cell-mediated immunity during Leishmania donovani infection[J].PLo S Pathog,2011,7(10):e1002279.
[7]Harrop JA,Mc Donnell PC,Brigham-Burke M,et al.Herpesvirus entry mediator ligand(HVEM-L),a novel ligand for HVEM/TR2,stimulates proliferation of T cells and inhibits HT29 cell growth[J].J Biol Chem,1998,273(42):27548-27556.
[8]Harrop JA,Reddy M,Dede K,et al.Antibodies to TR2(herpesvirus entry mediator),a new member of the TNF receptor superfamily,block T cell proliferation,expression of activation markers,and production of cytokines[J].J Immunol,1998,161(4):1786-1794.
[9]Krause P,Zahner SP,Kim G,et al.The tumor necrosis factor family member TNFSF14(LIGHT)is required for resolution of intestinal inflammation in mice[J].Gastroenterology,2014,146(7):1752-1762.
[10]Xu G,Liu D,Okwor I,et al.LIGHT Is critical for IL-12 production by dendritic cells,optimal CD4+Th1 cell response,and resistance to Leishmania major[J].J Immunol,2007,179(10):6901-6909.
[11]Heo SK,Ju SA,Lee SC,et al.LIGHT enhances the bactericidal activity of human monocytes and neutrophils via HVEM[J].J Leukocyte Biol,2006,79(2):330-338.
[12]Wang J,Lo JC,Foster A,et al.The regulation of T cell homeostasis and autoimmunity by T cell-derived LIGHT[J].J Clin Invest,2001,108(12):1771-1780.
[13]陈丽丽,孙源彬,徐莎,等.LIGHT信号通路在鼠衣原体生殖道感染中的作用[J].微生物学报,2015,55(4):365-373.
[14]Dutow P,Fehlhaber B,Bode J,et al.The complement C3a receptor is critical in defense against Chlamydia psittaci in mouse lung infection and required for antibody and optimal T cell response[J].J Infect Dis,2014,209(8):1269-1278.
[15]Ehlers S,Holscher C,Scheu S,et al.The lymphotoxinβreceptor is critically involved in controlling infections with the intracellular pathogens Mycobacterium tuberculosis and Listeria monocytogenes[J].J Immunol,2003,170(10):5210-5218.