Expansion of a subset of CD14highCD16negCCR2low/neg monocytes functionally similar to myeloid‐derived suppressor cells during SIV and HIV infection

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

关键词: macrophages;    AIDS;   

DOI  :  10.1189/jlb.1111579

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

MonocyteshavebeencategorizedinthreemainsubpopulationsbasedonCD14andCD16surfaceexpression.ClassicalmonocytesexpresstheCD14++CD16−CCR2+phenotypeandmigratetoinflammatorysitesbyquicklyrespondingtoCCL2signaling.Here,weidentifiedandcharacterizedtheexpansionofanovelmonocytesubsetduringHIVandSIVinfection,whichwereundistinguishablefromclassicalmonocytes,basedonCD14andCD16expression,butexpressedsignificantlylowersurfaceCCR2.TranscriptomeanalysisofsortedcellsdemonstratedthattheCCR2low/negcellsareadistinctsubpopulationandexpresslowerlevelsofinflammatorycytokinesandactivationmarkersthantheirCCR2highcounterparts.TheyexhibitedimpairedphagocytosisandgreatlydiminishedchemotaxisinresponsetoCCL2andCCL7.Inaddition,thesemonocytesarerefractorytoSIVinfectionandsuppressCD8+Tcellproliferationinvitro.ThesecellsexpresshigherlevelsofSTAT3andNOS2,suggestingaphenotypesimilartomonocyticmyeloid‐derivedcells,whichsuppressexpansionofCD8+Tcellsinvivo.TheymayreflectanantiproliferativeresponseagainsttheextremeimmuneactivationobservedduringHIVandSIVinfections.Inaddition,theymaysuppressantiviralresponsesandthus,havearoleinAIDSpathogenesis.Antiretroviraltherapyininfectedmacaqueandhumansubjectscausedthispopulationtodecline,suggestingthatthisatypicalphenotypeislinkedtoviralreplication...

【 授权许可】

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