Yersinia pestis survival and replication within human neutrophil phagosomes and uptake of infected neutrophils by macrophages

[摘要] Yersiniapestis,thebacterialagentofplague,istransmittedbyfleas.ThebiteofaninfectedfleadepositsY.pestisintothedermisandtriggersrecruitmentofinnateimmunecells,includingphagocyticPMNs.Y.pestiscansubvertthisPMNresponseandsurviveattheflea‐bitesite,disseminate,andpersistinthehost.Althoughitsgenomeencodesanumberofantiphagocyticvirulencefactors,phagocytosisofY.pestisbyPMNshasbeenobserved.ThisstudyteststhehypothesesthatY.pestis,grownattheambienttemperatureofthefleavector(21°C),wherethemajorantiphagocyticvirulencefactorsarenotproduced,cansurviveandreplicatewithinhumanPMNsandcanusePMNsasaroutetoinfectmacrophagessubsequently.WeshowthatY.pestisislocalizedwithinPMNphagosomes,predominatelyasindividualbacteria,andthatintracellularbacteriacansurviveandreplicate.Within12hofinfection,∼70%ofinfectedPMNshadPSontheirsurfaceandwereplausiblycompetentforefferocytosis.Withtheuseoflivecellconfocalimaging,weshowthatautologousHMDMsrecognizeandinternalizeinfectedPMNsandthatY.pestissurvivesandreplicateswithintheseHMDMsfollowingefferocytosis.AdditionofHMDMstoinfectedPMNsresultedindecreasedsecretionofinflammatorycytokines(comparedwithHMDMsincubateddirectlywithpCD1−Y.pestis)andincreasedsecretionoftheanti‐inflammatorycytokineIL‐1ra.Thus,Y.pestiscansurviveandreplicatewithinPMNs,andinfectedPMNsmaybearoutefornoninflammatoryinfectionofmacrophages...

[学科分类] 生理学

[关键词] polymorphonuclear leukocytes;phagocytosis;intracellular;apoptosis;efferocytosis