Original Encounter with Antigen Determines Antigen-Presenting Cell Imprinting of the Quality of the Immune Response in Mice 英文参考文献.docVIP

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Original Encounter with Antigen Determines Antigen-Presenting Cell Imprinting of the Quality of the Immune Response in Mice 英文参考文献.doc

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Original Encounter with Antigen Determines Antigen-Presenting Cell Imprinting of the Quality of the Immune Response in Mice 英文参考文献

OriginalEncounterwithAntigenDetermines Antigen-PresentingCellImprintingoftheQuality oftheImmuneResponseinMice Vale′rieAbadie1,2,3¤,OliviaBonduelle1,2,3,DarraghDuffy1,2,3,ChristopheParizot1,2,3,BernardVerrier4, Be′hazineCombadie`re1,2,3 * 1Institut National de la Sante′ et de la Recherche Me′dicale (INSERM) U945, Paris, France, 2University of Pierre and Marie Curie (UPMC)- Univ Paris 06, Paris, France, 3Assistance-Publique/Hopitaux-de-Paris,ImmunityandInfection,Paris,France,4InstitutdeBiologieetChimiedesProte′ines, UMR5086CNRS/UCBL,Lyon,France Abstract Background:Obtainingacertainmulti-functionalityofcellularimmunityforthecontrolofinfectiousdiseasesisaburning questioninimmunologyandinvaccinedesign.Earlyevents,includingantigenshuttlingtosecondarylymphoidorgansand recruitmentofinnateimmunecellsforadaptiveimmuneresponse,determinehostresponsivenesstoantigens.However, thesequenceoftheseeventsandtheirimpactonthequalityoftheimmuneresponseremaintobeelucidated.Here,we chosetostudyModifiedVacciniavirusAnkara(MVA)whichisnowreplacingliveSmallpoxvaccinesandisproposedasan attenuatedvectorforvaccinationstrategiesagainstinfectiousdiseases. Methodology/Principalfindings:Weanalyzedinvivomechanismstriggeredfollowingintradermal(i.d.)andintramuscular (i.m.)ModifiedVacciniavirusAnkara(MVA)administration.Wedemonstratedsignificantdifferencesintheantigenshuttling tolymphoidorgansbymacrophages(MWs),myeloiddendriticcells(DCs),andneutrophils(PMNs).MVAi.d.administration resultedinbetterantigendistributionandmoresustainedantigen-presentingcells(APCs)recruitmentintodraininglymph nodesthanwithi.m.administration.TheseAPCs,whichcomprisebothDCsandMWs,weredifferentiallyinvolvedinTcell primingandshapedremarkablythequalityofcytokine-producingvirus-specificTcellsaccordingtotheentryrouteofMVA. Conclusions/Significance: This study improves our understanding of the mechanisms of antigen delivery and their consequencesonthequalityofimmuneresponsesandprovidesnewinsightsforvaccinedevelopment. Citation: