Assessment of antibody‐dependent respiratory burst activity from mouse neutrophils on Plasmodium yoelii malaria challenge outcome

[摘要] Newtoolsarerequiredtoexpeditethedevelopmentofaneffectivevaccineagainsttheblood‐stageinfectionwiththehumanmalariaparasitePlasmodiumfalciparum.ThisworkdescribestheassessmentoftheADRBassayinamousemodel,characterizingthefunctionalinteractionbetweenantimalarialserumantibodiesandFcRsuponneutrophils.Wedescribeareproducible,antigen‐specificassay,dependentonfunctionalFcRsignaling,andshowthatADRBactivityisinducedequallybyIgG1andIgG2aisotypesandismodulatedbyblockingFcRfunction.However,followingimmunizationofmicewiththeblood‐stagevaccinecandidateantigenMSP142,nomeasurableADRBactivitywasinducedagainstPEMSandneitherwasvaccineefficacymodulatedagainstPlasmodiumyoeliiblood‐stagechallengeinγ−/−micecomparedwithWTmice.Incontrast,followingaprimary,nonlethalP.yoeliiparasitechallenge,serumfromvaccinatedmiceandnonimmunizedcontrolsshowedanti‐PEMSADRBactivity.Uponsecondarychallenge,nonimmunizedγ−/−miceshowedareducedabilitytocontrolblood‐stageparasitemiacomparedwithimmunizedγ−/−mice;however,WTmice,depletedoftheirneutrophils,didnotlosetheirabilitytocontrolinfection.Thus,whereasneutrophil‐inducedADRBagainstPEMSdoesnotappeartoplayaroleinprotectionagainstP.yoeliirodentmalaria,inductionofADRBactivityafterchallengesuggeststhatantigentargetsofanti‐PEMSADRBactivityremaintobeestablished,aswellasfurthersupportingtheobservationthatADRBactivitytoP.falciparumarisesfollowingrepeatednaturalexposure...

[学科分类] 生理学

[关键词] Fc receptor;vaccine;ROS;merozoite;assay;malaria;MSP1;neutrophil