Diversion of the host humoral response: a novel virulence mechanism of Haemophilus influenzae mediated via outer membrane vesicles

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

关键词: B cell;    immunoglobulin D;    nontypeable H. influenzae;    nanoparticles;    Toll‐;    like receptor;   

DOI  :  10.1189/jlb.1013527

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TherespiratorytractpathogenHaemophilusinfluenzaefrequentlycausesinfectionsinhumans.InparallelwithallGram‐negativebacteria,H.influenzaehasthecapacitytoreleaseOMV.Theproductionofthesenanoparticlesisanintriguingandpartlyunexploredphenomenoninpathogenesis.Here,weinvestigatedhowpurifiedhumanperipheralbloodBlymphocytesrespondtoOMVderivedfromunencapsulated,i.e.,NTHiandthenonpathogenicHaemophilusparainfluenzae.WefoundthatH.influenzaeOMVdirectlyinteractedwiththeIgDBCR,asrevealedbyanti‐IgDpAbandflowcytometry.Importantly,H.influenzaeOMV‐inducedcellularactivationviaIgDBCRcross‐linkingandTLR9resultedinasignificantproliferativeresponse.OMVisolatedfromtherelatedspeciesH.parainfluenzaedidnot,however,interactwithBcellsexcludingthattheeffectbyH.influenzaeOMVwaslinkedtocommonmembranecomponents,suchastheLOS.Wealsoobservedanup‐regulationofthecellsurfacemoleculesCD69andCD86,andanincreasedIgMandIgGsecretionbyBcellsincubatedwithH.influenzaeOMV.TheIgsproduceddidnotrecognizeH.influenzae,suggestingapolyclonalBcellactivation.Interestingly,thedensityofthecellsurfacereceptorTACIwasincreasedinthepresenceofOMVthatsensitizedfurthertheBcellstoBAFF,resultinginanenhancedIgGclass‐switch.Inconclusion,theabilityofNTHiOMVtoactivateBcellsinaTcell‐independentmannermaydiverttheadaptivehumoralimmuneresponsethatconsequentlypromotesbacterialsurvivalwithinthehumanhost...

【 授权许可】

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