The impact of α‐toxin on host cell plasma membrane permeability and cytokine expression during human blood infection by CA‐MRSA USA300

[摘要] Thisinvestigationexaminestheinfluenceofα‐toxin(Hla)expressionbyCA‐MRSAonhostimmunecellintegrityandcytokineexpressionduringinfectionofhumanblood.FlowcytometryanalysisofhumanbloodinfectedbyStaphylococcusaureusPFGEtypeUSA300oraUSA300ΔhlademonstratedthatHlaexpressionsignificantlyincreasedplasmamembranepermeabilityofhumanCD14+monocytes.TheincreasedsusceptibilityofhumanCD14+monocytestoHlatoxicityparalleledthehighcell‐surfaceexpressiononthesecelltypesofADAM10.USA300rapidlyassociatedwithPMNsandmonocytesbutnotTcellsfollowinginoculationofhumanblood.Transcriptionanalysisindicatedastrongup‐regulationofproinflammatorycytokinetranscriptionfollowinginfectionofhumanbloodbyUSA300andUSA300Δhla.CBAsandELISAsdeterminedthatIL‐6,IL‐10,TNF‐α,IFN‐γ,IL‐1β,IL‐8,andIL‐4aresignificantlyup‐regulatedduringtheinitialphasesofhumanbloodinfectionbyUSA300relativetomock‐infectedbloodbutfailedtodistinguishanysignificantdifferencesinsecretedcytokineproteinconcentrationsduringinfectionbyUSA300ΔhlarelativetoUSA300.Collectively,thesefindingsdemonstratethatexpressionofHlabyUSA300hasasignificantimpactonhumanCD14+monocyteplasmamembraneintegritybutisnotexclusivelyresponsiblefortheproinflammatorycytokineprofileinducedbyUSA300duringtheinitialstagesofhumanbloodinfection...

[学科分类] 生理学

[关键词] Staphylococcus aureus pathogenesis;virulence;monocyte;T cell;chemokine