Mycobacterium tuberculosis Lineage Influences Innate Immune Response and Virulence and Is Associated with Distinct Cell Envelope Lipid Profiles 英文参考文献.docVIP

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Mycobacterium tuberculosis Lineage Influences Innate Immune Response and Virulence and Is Associated with Distinct Cell Envelope Lipid Profiles 英文参考文献.doc

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Mycobacterium tuberculosis Lineage Influences Innate Immune Response and Virulence and Is Associated with Distinct Cell Envelope Lipid Profiles 英文参考文献

MycobacteriumtuberculosisLineageInfluencesInnate ImmuneResponseandVirulenceandIsAssociatedwith DistinctCellEnvelopeLipidProfiles NityaKrishnan1,WladimirMalaga2,3,PatriciaConstant2,3,MaxineCaws4,TranThiHoangChau5 ,Jenifer Salmons1,NguyenThiNgocLan6,NguyenDucBang6,MamadouDaffe′2,3,DouglasB.Young1,7,BrianD. Robertson1,ChristopheGuilhot2,3,GuyE.Thwaites1* 1CentreforMolecularMicrobiologyandInfection,ImperialCollegeLondon,London,UnitedKingdom,2CNRS,IPBS(InstitutdePharmacologieetdeBiologieStructurale), Toulouse,France, 3Universite′ de Toulouse, UPS, IPBS, Toulouse, France, 4Oxford University Clinical Research Unit, HoChi MinhCity, Vietnam, 5Hospital for Tropical Diseases,HoChiMinhCity,Vietnam,6PhamNgocThachHospitalforTuberculosisandLungDisease,HoChiMinhCity,Vietnam,7NationalInstituteforMedicalResearch, London,UnitedKingdom Abstract ThesixmajorgeneticlineagesofMycobacteriumtuberculosisarestronglyassociatedwithspecificgeographicalregions,but their relevance to bacterial virulence and the clinical consequences of infection are unclear. Previously, we found that in Vietnam,EastAsian/BeijingandIndo-Oceanicstrainsweresignificantlymorelikelytocausedisseminatedtuberculosiswith meningitisthanthosefromtheEuro-Americanlineage.Toinvestigatethisobservationwecharacterised7EastAsian/Beijing,5 Indo-Oceanicand6Euro-AmericanVietnamesestrainsinbone-marrow-derivedmacrophages,dendriticcellsandmice.East Asian/BeijingandIndo-OceanicstrainsinducedsignificantlymoreTNF-aandIL-1bfrommacrophagesthantheEuro-American strains,andEastAsian/Beijingstrainsweredetectableearlierinthebloodofinfectedmiceandgrewfasterinthelungs.We hypothesisedthatthesedifferenceswereinducedbylineage-specificvariationincellenvelopelipids.Wholelipidextractsfrom EastAsian/BeijingandIndo-OceanicstrainsinducedhigherconcentrationsofTNF-afrommacrophagesthanEuro-American lipids.Thelipidextractswerefractionatedandcomparedbythinlayerchromatographytorevealadistinctpatternoflineage- associatedprofiles.Aphthiotrioldimycocerosatewasexclusi