CCL5 participates in early protection against Mycobacterium tuberculosis

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

关键词: chemokine;    granuloma;    pulmonary;    murine;   

DOI  :  10.1189/jlb.1109742

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ControlofM.tb,thecausativeagentofTB,requiresimmunecellrecruitmenttoformlunggranulomas.Thechemokinesandchemokinereceptorsthatpromotecellmigrationforgranulomaformation,however,arenotdefinedcompletely.AsimmunitytoM.tbmanifestsslowlyinthelungs,abetterunderstandingofspecificrolesforchemokines,inparticularthosethatpromoteM.tb‐protectiveTH1responses,mayidentifytargetsthatcouldaccelerategranulomaformation.ThechemokineCCL5hasbeendetectedinpatientswithTBandimplicatedincontrolofM.tbinfection.TodefinearoleforCCL5invivoduringM.tbinfection,CCL5KOmicewereinfectedwithalowdoseofaerosolizedM.tb.DuringearlyM.tbinfection,CCL5KOmicelocalizedfewerAPCsandchemokinereceptor‐positiveTcellstothelungsandhadmicroscopicevidenceofalteredcelltraffickingtoM.tbgranulomas.EarlyacquiredimmunityandgranulomafunctionweretransientlyimpairedwhenCCL5wasabsent,evidentbydelayedIFN‐γresponsesandpoorcontrolofM.tbgrowth.LungcellsfromM.tb‐infectedCCL5KOmiceeventuallyreachedorexceededthelevelsofWTmice,likelyasaresultofpartialcompensationbytheCCL5‐relatedligand,CCL4,andnotbecauseofCCL3.Finally,ourresultssuggestthatmostTcellsuseCCR5butnotCCR1tointeractwiththeseligands.Overall,theseresultscontributetoamodelofM.tbgranulomaformationdependentontemporalregulationofchemokinesratherthanonredundantorpromiscuousinteractions...

【 授权许可】

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