Dissection of the Role of PfEMP1 and ICAM-1 in the Sensing of Plasmodium falciparum-Infected Erythrocytes by Natural Killer Cells 英文参考文献.docVIP

DissectionoftheRoleofPfEMP1andICAM-1inthe SensingofPlasmodiumfalciparum-InfectedErythrocytes byNaturalKillerCells MyriamBaratin1,2,3.,SophieRoetynck1,2,3.,BrunoPouvelle4,Ce′lineLemmers1,2,3,NicolaK.Viebig5,SofiaJohansson1,2,3,PhilippeBierling6, ArturScherf5,Ju¨rgGysin4,EricVivier1,2,3,7*,SophieUgolini1,2,3 * 1Aix-MarseilleUniversite′,Faculte′desSciencesdeLuminy,Centred’ImmunologiedeMarseille-Luminy(CIML),Marseille,France,2InstitutNationalde laSante′ etdelaRechercheMe′dicale (INSERM),U631,Marseille,France,3CentreNationaldelaRechercheScientifique(CNRS),UMR6102,Marseille, France,4Unite′deParasitologieExpe′rimentale,Universite′delaMe′diterrane′e,Marseille,France,5InstitutPasteurandCentreNationaldelaRecherche Scientifique(CNRS),Paris,France,6Etablissementfranc?ais dusang,Cre′teil,France,7Ho?pitaldelaConception,AssistancePublique–Ho?pitauxde Marseille,France Background.Hostinnateimmunitycontributestomalariaclinicaloutcomebyprovidingprotectiveinflammatorycytokines suchasinterferon-c,andbyshapingtheadaptiveimmuneresponse.Plasmodiumfalciparum(Pf)istheetiologicagentofthe mostsevereformsofhumanmalaria.NaturalKiller(NK)cellsarelymphocytesoftheinnateimmunesystemthatarethefirst effectors to produce interferon-c in response to Pf. However, the molecular bases of Pf-NK cell recognition events are unknown.OurstudyfocusesontheroleofPferythrocytemembraneprotein1(PfEMP1),amajorPfvirulencefactor.PfEMP1is expressedonparasitized-erythrocytesandparticipatestovascularobstructionthroughthebindingtoseveralhostreceptors. PfEMP1 is also a pivotal target for host antibody response to Pf infection. Methodology/Principal Findings. Using genetically-engineered parasite mutant strains, a human genetic deficiency, and blocking antibodies, we identified two receptor-ligandpairsinvolvedintwouncoupledeventsoccurringduringthesensingofPfinfectionbyNKcells.First,PfEMP1 interaction with one of its host receptor, chondroitin sulfate A, mediates the cytoadhesion of Pf-infected erythrocytes to human NK