Relative Roles of the Cellular and Humoral Responses in the Drosophila Host Defense against Three Gram-Positive Bacterial Infections 英文参考文献.docVIP

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Relative Roles of the Cellular and Humoral Responses in the Drosophila Host Defense against Three Gram-Positive Bacterial Infections 英文参考文献.doc

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Relative Roles of the Cellular and Humoral Responses in the Drosophila Host Defense against Three Gram-Positive Bacterial Infections 英文参考文献

RelativeRolesoftheCellularandHumoralResponsesin theDrosophilaHostDefenseagainstThree Gram-PositiveBacterialInfections NadineT.Nehme1.¤a,JessicaQuintin1.,JuHyunCho1,2¤b,JaniceLee1,2,Marie-Ce′lineLafarge1 ,Christine Kocks1,2,DominiqueFerrandon1* 1Equipe Fondation Recherche Me′dicale, UPR 9022 du Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Mole′culaire et Cellulaire du CNRS, Universite′ deStrasbourg,Strasbourg,France,2DepartmentofPediatrics,MassachusettsGeneralHospital,HarvardMedicalSchool,Boston,Massachusetts,UnitedStates ofAmerica Abstract Background: Two NF-kappaB signaling pathways, Toll and immune deficiency (imd), are required for survival to bacterial infectionsinDrosophila.Inresponsetosepticinjury,thesepathwaysmediaterapidtranscriptionalactivationofdistinctsets ofeffectormolecules,includingantimicrobialpeptides,whichareimportantcomponentsofahumoraldefenseresponse. However,itislesscleartowhatextentmacrophage-likehemocytescontributetohostdefense. Methodology/PrincipalFindings:Inordertodissecttherelativeimportanceofhumoralandcellulardefensesafterseptic injurywiththreedifferentGram-positivebacteria(Micrococcusluteus,Enterococcusfaecalis,Staphylococcusaureus),weused latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival – independentlyofconcomitantTollorimdpathwayactivation.OurdatafailedtoconfirmaroleofthePGRP-SAandGNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosisbyhemocytesorS2cellsofE.faecalisandS.aureus,butnotofM.luteus.InthecaseofM.luteusandE.faecalis, butnotS.aureus,decreasedsurvivalduetodefectivephagocytosiscouldbecompensatedforbygeneticallyenhancingthe humoralimmuneresponse. Conclusions/Significance:Ourresultsunderscorethefundamentalimportanceofbothcellularandhumoralmechanismsi