Protective Immunity to Mycobacterium tuberculosis Infection by Chemokine and Cytokine Conditioned CFP-10 Differentiated Dendritic Cells 英文参考文献.docVIP

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Protective Immunity to Mycobacterium tuberculosis Infection by Chemokine and Cytokine Conditioned CFP-10 Differentiated Dendritic Cells 英文参考文献.doc

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Protective Immunity to Mycobacterium tuberculosis Infection by Chemokine and Cytokine Conditioned CFP-10 Differentiated Dendritic Cells 英文参考文献

ProtectiveImmunitytoMycobacteriumtuberculosis InfectionbyChemokineandCytokineConditionedCFP- 10DifferentiatedDendriticCells NasirSalam1,ShashankGupta1,SachinSharma1,ShwetaPahujani1,AprajitaSinha1,RajivK.Saxena2, KrishnamurthyNatarajan1* 1ImmunologyGroup,InternationalCentreforGeneticEngineeringandBiotechnology,ArunaAsafAliMarg,NewDelhi,India,2SchoolofLifeSciences,JawaharlalNehru University,NewDelhi,India Abstract Background:Dendriticcells(DCs)playmajorrolesinmediatingimmuneresponsestomycobacteria.Acrucialaspectofthis istheprimingofTcellsviachemokinesandcytokines.InthisstudyweinvestigatedtherolesofchemokinesRANTESandIP- 10inregulatingprotectiveresponses fromMycobacterium tuberculosis (M.tb)10kDaCultureFiltrateProtein-10(CFP-10) differentiatedDCs(CFP10-DCs). Methods and Findings: Infection of CFP10-DCs with mycobacteria down-modulated RANTES and IP-10 levels. Pathway specific microarray analyses showed that in addition to RANTES and IP-10, mycobacteria infected CFP10-DCs showed reduced expression of many Th1 promoting chemokines and chemokine receptors. Importantly, T cells co-cultured with RANTESandIP-10conditionedCFP10-DCsmediatedkillingofmycobacteriafrominfectedmacrophages.Similarly,Tcells recruited by RANTES and IP-10 conditioned CFP10-DCs mediated significant killing of mycobacteria from infected macrophages. IFN-gamma treatment of CFP10-DCs restored RANTES and IP-10 levels and T cells activated by these DCs mediatedsignificantkillingofvirulentM.tbinsidemacrophages.AdoptivetransferofeitherRANTESandIP-10orIL-12and IFN-gammaconditionedCFP10-DCsclearedanestablishedM.tbinfectioninmice.Theextentofclearancewassimilarto thatobtainedwithdrugtreatment. Conclusions:TheseresultsindicatethatchemokineandcytokinesecretionbyDCsdifferentiatedbyM.tbantigenssuchas CFP-10playmajorrolesinregulatingprotectiveimmuneresponsesatsitesofinfection. Citation:SalamN,GuptaS,SharmaS,PahujaniS,SinhaA,etal.(2008)ProtectiveImmunitytoMycobacteriumtuberculosisInfectionbyChemokineandCytokine Cond