Mycobacterium tuberculosis RpfB drives Th1‐type T cell immunity via a TLR4‐dependent activation of dendritic cells

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: GATA‐;    3;    T‐;    bet;    Vaccine;   

DOI  :  10.1189/jlb.0912435

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ThefailureofMycobacteriumbovisBCGasaTBvaccineagainstTBreactivationsuggeststhatlatency‐associatedproteinsshouldbeincludedinalternativeTBvaccinedevelopment.Further,antigensknowntogenerateprotectiveimmunityagainstthestrongTh1stimulatoryresponsetoreactivatedTBshouldbeincludedinnovelvaccinedesign.RecentstudieshaveemphasizedtheimportanceofRpfsfromMycobacteriumtuberculosisinthereactivationprocessandcellularimmunity.However,littleisknownabouthowRpfBmediatesprotectiveimmunityagainstM.tuberculosis.Here,weinvestigatedthefunctionalrolesandsignalingmechanismsofRpfBinDCsanditsimplicationsinthedevelopmentofTcellimmunity.DCstreatedwithRpfBdisplayedfeaturesofmatureandfunctionalstatus,withelevatedexpressionofcellsurfacemolecules(CD80,CD86,andMHCclassIandII)andproinflammatorycytokineproduction(TNF‐α,IL‐1β,IL‐6,andIL‐12p70).ActivationofDCswasmediatedbydirectbindingofRpfBtoTLR4,followedbyMyD88/TRIF‐dependentsignalingtoMAPKsandNF‐κBsignalingpathways.Specifically,wefoundthattheRpfBG5domainisthemostimportantpartinRpfBbindingtoTLR4.RpfB‐treatedDCseffectivelypolarizednaïveCD4+andCD8+TcellstosecreteIFN‐γandIL‐2.Importantly,RpfBinducedtheexpansionofmemoryCD4+/CD8+CD44highCD62LlowTcellsinthespleenofM.tuberculosis‐infectedmice.OurdatasuggestthatRpfBregulatesinnateimmunityandactivatesadaptiveimmunitythroughTLR4,afindingthatmayhelpinthedesignofmoreeffectivevaccines...

【 授权许可】

CC BY