Mycobacterium indicus pranii induces dendritic cell activation, survival, and Th1/Th17 polarization potential in a TLR‐dependent manner

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

关键词: cytokines;    costimulatory molecules;    apoptosis;    T cell polarization;    pattern recognition receptors;   

DOI  :  10.1189/jlb.1A0714-361R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

MIPisanonpathogenic,soil‐bornepredecessorofMycobacteriumavium.IthasbeenreportedpreviouslythatMIPpossessesstrongimmunomodulatorypropertiesandconfersprotectionagainstexperimentalTBandtumor.DCs,byvirtueoftheirunmatchedantigen‐presentationpotential,playacriticalroleinactivationofantitumorandantimycobacterialimmuneresponse.TheeffectofMIPonthebehaviorofDCsandtheunderlyingmechanisms,however,havenotbeeninvestigatedsofar.Inthepresentstudy,weshowedthatMIPinducessignificantsecretionofIL‐6,IL‐12p40,IL‐10,andTNF‐αbyDCsandup‐regulatestheexpressionofcostimulatorymoleculesCD40,CD80,andCD86.MIP(L)inducedasignificantlyhigherresponsecomparedwithMIP(K).PIandAnnexinVstainingshowedthatMIPincreasesDCsurvivalbyinhibitingapoptosis.Consistently,higherexpressionofantiapoptoticproteinsBcl‐2andBcl‐xlwasobservedinMIP‐stimulatedDCs.Cytokines,producedbynai¨veTcells,coculturedwithMIP‐stimulatedDCs,showedthatMIPpromotesTh1/Th17polarizationpotentialinDCs.ResponsetoMIPwaslostinMyD88−/−DCs,underscoringthecriticalroleofTLRsinMIP‐inducedDCactivation.FurtherstudiesrevealedthatTLR2andTLR9areinvolvedinDCactivationbyMIP(L),whereasMIP(K)activatestheDCsthroughTLR2.OurfindingsestablishtheDCactivationbyMIP,definethebehaviorofMIP‐stimulatedDCs,andhighlighttheroleofTLRsinMIP‐inducedDCactivation...

【 授权许可】

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