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

[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...

[学科分类] 生理学

[关键词] Lyme disease;immunosuppression;bacterium;dendritic cells