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

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: ranavirus;    FV3;    immunity;    CSF‐;    1;    IL‐;    34;   

DOI  :  10.1189/jlb.4A0614-295R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 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...

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