BTLA expression contributes to septic morbidity and mortality by inducing innate inflammatory cell dysfunction

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: HVEM;    sepsis;    macrophage;    monocyte;    neutrophil;    IL‐;    10;   

DOI  :  10.1189/jlb.1211641

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Aproperinnateinflammatoryresponseisessentialforpreventionofthesystemicinflammationassociatedwithsepsis.BTLAisanimmune‐regulatoryreceptordemonstratedtobeexpressednotonlyonadaptiveimmunepopulationsandhavepotentinhibitoryeffectsonCD4+Tcellsbutisalsoexpressedoninnatecellpopulations(CD11c+andCD11b+cells)andhasbeenshowntodiminishpathogenclearancefollowingbacterialandparasiteinfection.TheroleofBTLAinsepsisandthemechanismsbywhichBTLAalterspathogenclearance,however,havenotbeenaddressedclearly.Here,weshowthatfollowingacuteexperimentalsepsisinductioninmice(CLP),thenumberofinfiltratingBTLA‐andHVEM(theligandforBTLA)‐expressingmacrophages,inflammatorymonocytes,matureandimmatureDCs,andneutrophilsincreasedintheperitoneumcomparedwithshamsurgery,suggestingthatahighlevelofHVEM:BTLAinteractionsoccursbetweenthesecellsatthesiteofsepticinsult.Giventhis,weevaluatedBTLA−/−mice,24hpost‐CLP,andobservedamarkedincreaseinthedegreeofactivationonthesecellpopulations,aswellasareductioninperitonealbacterialburdenandIL‐10induction,andmostimportantly,BTLA−/−miceexhibitedahigherrateofsurvivalandprotectionfromorganinjurywhencomparedwithWTmice.Suchchangeswerenotrestrictedtoexperimentalmice,ascirculatingBTLA+andHVEM+monocytesandHVEM+granulocyteswereincreasedinsepticICUpatients,supportingaroleforBTLAand/orHVEMaspotential,noveldiagnosticmarkersofinnateimmuneresponse/statusandastherapeutictargetsofsepsis...

【 授权许可】

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