Induction of indoleamine 2,3‐dioxygenase by Borrelia burgdorferi in human immune cells correlates with pathogenic potential

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

关键词: Lyme disease;    immunosuppression;    bacterium;    dendritic cells;   

DOI  :  10.1189/jlb.4A0714-339R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Borreliaburgdorferi,thebacterialagentofLymedisease,inducestheproductionoftypeIIFNsbyhumanDCsthroughTLR7andTLR9signaling.ThistypeIIFNresponseoccursinagenotype‐dependentmanner,withsignificantlyhigherlevelsofIFN‐αelicitedbyB.burgdorferistrainsthathaveagreatercapacityforcausingdisseminatedinfection.AB.burgdorferistrainthatwaspreviouslyshowntoinduceIFN‐αwasfoundtoelicitsignificantlyhigherlevelsofIDO1proteinanditsdownstreammetabolite,kynurenine,comparedwithaB.burgdorferimutantthatlacksasinglelinearplasmid(lp36);thismutantisunabletoinduceIFN‐αandisseverelyattenuatedforinfectivityinmice.ProductionofIDObymDCandpDCpopulations,presentwithinhumanPBMCs,wasconcomitantwithincreasedexpressionoftheDCmaturationmarkers,CD83andCCR7.ThedefectsinIDOproductionandexpressionofCD83andCCR7couldberestoredbycomplementationofthemutantwithlp36.MaximalIDOproductioninresponsetothewild‐typestrainwasdependentoncontributionsbybothtypeIIFNandIFN‐γ,thetypeIIIFN.InductionofIDOwasmediatedbythesameTLR7‐dependentrecognitionofB.burgdorferiRNAthatcontributestotheproductionoftypeIIFNsbyhumanDCs.TheabilityofIFN‐α‐inducingB.burgdorferistrainstostimulateproductionofIDOandkynureninesmaybeamechanismthatisusedbythepathogentopromotelocalizedimmunosuppressionandfacilitatehematogenousdissemination...

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