MyD88-Dependent Signaling Influences Fibrosis and Alternative Macrophage Activation during Staphylococcus aureus Biofilm Infection 英文参考文献.doc

MyD88-DependentSignalingInfluencesFibrosisand AlternativeMacrophageActivationduring StaphylococcusaureusBiofilmInfection MarkL.Hanke,AmandaAngle,TammyKielian* DepartmentofPathologyandMicrobiology,UniversityofNebraskaMedicalCenter,Omaha,Nebraska,UnitedStatesofAmerica Abstract Bacterialbiofilmsrepresentasignificanttherapeuticchallengebasedontheirabilitytoevadehostimmuneandantibiotic- mediatedclearance.RecentstudieshaveimplicatedIL-1binbiofilmcontainment,whereasToll-likereceptors(TLRs)hadno effect. This is intriguing, since both the IL-1 receptor (IL-1R) and most TLRs impinge on MyD88-dependent signaling pathways,yettheroleofthiskeyadaptorinmodulatingthehostresponsetobiofilmgrowthisunknown.Therefore,we examinedthecourseofS.aureuscatheter-associatedbiofilminfectioninMyD88knockout(KO)mice.MyD88KOanimals displayed significantly increased bacterial burdens on catheters and surrounding tissues during early infection, which coincidedwithenhanceddisseminationtotheheartandkidneycomparedtowildtype(WT)mice.Theexpressionofseveral proinflammatorymediators,includingIL-6,IFN-c,andCXCL1wassignificantlyreducedinMyD88KOmice,primarilyatthe laterstagesofinfection.Interestingly,immunofluorescencestainingofbiofilm-infectedtissuesrevealedincreasedfibrosisin MyD88KOmiceconcomitantwithenhancedrecruitmentofalternativelyactivatedM2macrophages.Takeninthecontext ofpreviousstudieswithIL-1b,TLR2,andTLR9KOmice,thecurrentreportrevealsthatMyD88signalingisamajoreffector pathway regulating fibrosis and macrophage polarization during biofilm formation. Together these findings represent anovelexampleofthedivergencebetweenTLRandMyD88actioninthecontextofS.aureusbiofilminfection. Citation: Hanke ML, Angle A, Kielian T(2012) MyD88-Dependent Signaling Influences Fibrosis and AlternativeMacrophage Activation during Staphylococcus aureusBiofilmInfection.PLoSONE7(8):e42476.doi:10.1371/journal.pone.0042476 Editor:DipshikhaChakravortty,IndianInstituteofScience,India ReceivedFebruary27,2012;AcceptedJuly9,2012;Pub