Distinct functional roles of amphibian (Xenopus laevis) colony‐stimulating factor‐1‐ and interleukin‐34‐derived macrophages

[摘要] AlthoughMϕrepresentthemostprimordialimmunecellsubsets,themechanismsgoverningtheirfunctionalheterogeneityremainpoorlydefined.However,itiswellestablishedthattheCSF‐1cytokinecontributestomonopoiesisandtothisheterogeneity,whereastheunrelatedIL‐34alsobindstheCSF‐1Rtowardpoorlyunderstoodimmunologicroles.TodelineatethemolecularandevolutionarybasisbehindvertebrateMϕfunctionalheterogeneity,weperformedcomprehensivetranscriptionalandfunctionalstudiesofamphibian(Xenopuslaevis)BM(invitro)andPER(invivo)MϕderivedbyrXlCSF‐1andrXlIL‐34.OurfindingsindicatethattheseamphibiancytokinespromotemorphologicallyandfunctionallydistinctMϕpopulations.MϕinducedbyrXlCSF‐1possessmorerobustiNOSgeneexpression,aresubstantiallymorephagocytic,displaygreaterNOresponses,andexhibitenhancedbactericidalcapacities.Bycontrast,rXlIL‐34‐derivedMϕexpressgreaterlevelsofArg‐1andNADPHoxidasecomponentsandpossessgreaterrespiratoryburstresponses.Mostnotably,whereasCSF‐1MϕarehighlysusceptibletotheemergingFV3ranavirus,rXlIL‐34Mϕexhibitpotentantiviralactivityagainstthispathogen,whichisdependentonreactiveoxygenproduction.ThisworkmarksanadvanceinourunderstandingofthepossiblemechanismsgoverningvertebrateMϕfunctionalheterogeneity...

[学科分类] 生理学

[关键词] antimicrobial response;CSF‐1;IL‐34;ranavirus;myelopoiesis