Sublytic concentrations of Staphylococcus aureus Panton‐Valentine leukocidin alter human PMN gene expression and enhance bactericidal capacity

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

关键词: MRSA;    priming;    neutrophil;   

DOI  :  10.1189/jlb.1111575

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

CA‐MRSAinfectionsareoftencausedbystrainsencodingPVL,whichcancauselysisofPMNsandothermyeloidcellsinvitro,afunctionconsideredwidelyastheprimarymeansbywhichPVLmightcontributetodisease.However,atsublyticconcentrations,PVLcanfunctionasaPMNagonist.Tobetterunderstandthisphenomenon,weinvestigatedtheabilityofPVLtoalterhumanPMNfunction.PMNsexposedtoPVLhadenhancedcapacitytoproduceO2−inresponsetofMLF,butunlikeprimingbyLPS,thisresponsedidnotrequireTLRsignaltransduction.Ontheotherhand,therewassubcellularredistributionofNADPHoxidasecomponentsinPMNsfollowingexposureofthesecellstoPVL—afindingconsistentwithpriming.Importantly,PMNsprimedwithPVLhadanenhancedabilitytobind/ingestandkillStaphylococcusaureus.PrimingofPMNswithotheragonists,suchasIL‐8orGM‐CSF,alteredtheabilityofPVLtocauseformationofporesintheplasmamembranesofthesecells.MicroarrayanalysisrevealedsignificantchangesinthehumanPMNtranscriptomefollowingexposuretoPVL,includingup‐regulationofmoleculesthatregulatetheinflammatoryresponse.Consistentwiththemicroarraydata,mediatorsoftheinflammatoryresponsewerereleasedfromPMNsafterstimulationwithPVL.WeconcludethatexposureofhumanPMNstosublyticconcentrationsofPVLelicitsaproinflammatoryresponsethatisregulatedinpartatthelevelofgeneexpression.WeproposethatPVL‐mediatedprimingofPMNsenhancesthehostinnateimmuneresponse...

【 授权许可】

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