Divergent antiviral roles of amphibian (Xenopus laevis) macrophages elicited by colony‐stimulating factor‐1 and interleukin‐34

[摘要] MacrophagesareintegraltoamphibianimmunityagainstRVs,aswellastotheinfectionstrategiesofthesepathogens.AlthoughCSF‐1wasconsideredtobetheprincipalmediatorofmacrophagedevelopment,theIL‐34cytokine,whichsharesnosequenceidentitywithCSF‐1,isnowbelievedtocontributetovertebratemonopoiesis.However,therespectiverolesofCSF‐1‐andIL‐34‐derivedmacrophagesarestillpoorlyunderstood.TodelineatethecontributionofthesemacrophagepopulationstoamphibianimmunityagainsttheRVFV3,weidentifiedtheXenopuslaevisIL‐34andtranscriptionallyandfunctionallycomparedthiscytokinewiththepreviouslyidentifiedX.laevisCSF‐1.TheX.laevisCSF‐1andIL‐34displayedstrikinglynonoverlappingdevelopmentalandtissue‐specificgene‐expressionpatterns.Furthermore,onlyCSF‐1butnotIL‐34wasup‐regulatedinthekidneysofFV3‐challengedtadpoles.Intriguingly,recombinantformsofthesecytokines(rXlCSF‐1,rXlIL‐34)elicitedmorphologicallydistincttadpolemacrophages,andwhereasrXlCSF‐1pretreatmentdecreasedthesurvivalofFV3‐infectedtadpoles,rXlIL‐34administrationsignificantlyprolongedFV3‐challengedanimalsurvival.ComparedwithrXlIL‐34‐elicitedmacrophages,macrophagesderivedbyrXlCSF‐1weremorephagocyticbutalsosignificantlymoresusceptibletoinvitroFV3infections.Bycontrast,rXlIL‐34‐derivedmacrophagesexhibitedsignificantlygreaterinvitroantiranaviralactivityanddisplayedsubstantiallymorerobustgeneexpressionoftheNADPHoxidasecomponents(p67phox,gp91phox)andtypeIIFN.Moreover,FV3‐challenged,rXlIL‐34‐derivedmacrophagesexhibitedseveralordersofmagnitudegreaterup‐regulationofthetypeIIFNgeneexpression.ThismarksthefirstreportofthedisparaterolesofCSF‐1andIL‐34invertebrateantiviralimmunity...

[学科分类] 生理学

[关键词] ranavirus;FV3;immunity;CSF‐1;IL‐34