Fas regulates neutrophil lifespan during viral and bacterial infection

[摘要] Theregulationofneutrophillifespaniscriticalforacircumscribedimmuneresponse.NeutrophilsaresensitivetoFas/CD95deathreceptorsignalinginvitro,butitisunknownifFasregulatesneutrophillifespaninvivo.WehypothesizedthatFasL‐expressingCD8+Tcells,whichkillantigen‐stimulatedTcellsduringchronicviralinfection,canalsoinduceneutrophildeathintissuesduringinfection.WiththeuseofLysM‐CreFasfl/flmice,whichlackFasexpressioninmacrophagesandneutrophils,weshowthatFasregulatesneutrophillifespanduringlymphocyticchoriomeningitisvirus(LCMV)infectioninthelung,peripheralblood,andspleen.FasalsocontributedtotheregulationofneutrophilnumbersinthecolonofCitrobacterrodentium‐infectedmice.ToexaminetheeffectsofinfectiononFasactivationinneutrophils,weprimedneutrophilswithTLRligandsorIL‐18,resultinginablationofFasdeathreceptorsignaling.ThesedataprovidethefirstinvivogeneticevidencethatneutrophillifespaniscontrolledbydeathreceptorsignalingandprovideamechanismtoaccountforneutrophilresistancetoFasstimulationduringinfection...

[学科分类] 生理学

[关键词] apoptosis;TLR;IL‐18;LCMV;Citrobacter rodentium