Involvement of TLR2 and TLR4 in cell responses to Rickettsia akari

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

关键词: innate immunity;    Toll‐;    like receptors;    signal transduction;    cell activation;    monocytes/macrophages;   

DOI  :  10.1189/jlb.1009674

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Abetterunderstandingofthepathogenesisofrickettsialdiseaserequireselucidationofmechanismsgoverninghostdefenseduringinfection.TLRsareprimarysensorsofmicrobialpathogensthatactivateinnateimmunecells,aswellasinitiateandorchestrateadaptiveimmuneresponses.However,theroleofTLRsinrickettsiarecognitionandcellactivationremainspoorlyunderstood.Inthisstudy,weexaminedtheinvolvementofTLR2andTLR4inrecognitionofRickettsiaakari,acausativeagentofrickettsialpox.Transfection‐basedcomplementationofTLR2/4‐negativeHEK293TcellswithhumanTLR2orTLR4coexpressedwithCD14andMD‐2enabledIκB‐αdegradation,NF‐κBreporteractivation,andIL‐8expressioninresponsetoheat‐killed(HK)R.akari.ThepresenceoftheR753QTLR2orD299GTLR4polymorphismssignificantlyimpairedthecapacitiesoftherespectiveTLRstosignalHKR.akari‐mediatedNF‐κBreporteractivationinHEK293Ttransfectants.BlockingAbagainstTLR2orTLR4markedlyinhibitedTNF‐αreleasefromhumanmonocytesstimulatedwithHKR.akari,andTNF‐αsecretionelicitedbyinfectionwithliveR.akariwasreducedsignificantlyonlyuponblockingofTLR2andTLR4.LiveandHKR.akariexertedphosphorylationofIRAK1andp38MAPKin293/TLR4/MD‐2or293/TLR2stablecelllines,whereasonlylivebacteriaelicitedresponsesinTLR2/4‐negativeHEK293Tcells.ThesedatademonstratethatHKR.akaritriggerscellactivationviaTLR2orTLR4andsuggestuseofadditionalTLRsand/orNLRsbyliveR.akari...

【 授权许可】

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