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

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...