HIV‐1 gp120 signaling through TLR4 modulates innate immune activation in human macrophages and the biology of hepatic stellate cells

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

关键词: AIDS;    receptor;    cytokine;    chemokine;    migration;   

DOI  :  10.1189/jlb.4A1215-534R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

HighlyactiveantiretroviraltherapyhassignificantlyimprovedtheprognosisofHIV‐infectedsubjects.However,patientstreatedlongtermstillmanifestincreasedmortalityand,evenwithundetectableplasmaviremia,oftenexperiencepersistentimmuneactivation.Furthermore,liver‐relatedmortalityisnowthemostcommoncauseofnon‐AIDS‐relateddeathinHIV‐infectedindividualsonhighlyactiveantiretroviraltherapythroughacceleratedfibrosisprogression.TLRsarethefirstlineofthehostresponsetopathogensandplayanimportantroleinhumanhostdefenseagainstvirusesthroughsensingofviralstructuralproteins.GrowingevidencepointstoTLR4asakeyplayerinchronicimmuneactivation,HIVrecognition/replication,andliverfibrosisprogression,suggestingthatHIVtriggeringofTLR4maydictatesomeaspectsofthemultifacetedAIDSpathogenesis.Inthisstudy,weprovideevidenceforaninterplaybetweenhostTLR4andHIV‐1gp120inhumanmonocyte‐derivedmacrophagesandhepaticstellatecells,leadingtointracellularpathwaysandbiologicactivitiesthatmediateproinflammatoryandprofibrogenicsignals.Finally,wehypothesizethatCCR5andTLR4arelikelypartofacommonreceptorcluster,astheblockingofCCR5byspecificantagonistsimpairsthemacrophagecapacitytoproducechemokinesinresponsetoLPS.Chronicimmuneactivationandliverfibrosisremainimportantobstaclesforhighlyactiveantiretroviraltherapysuccess.Thus,theidentificationofgp120‐TLR4axisasanoveldeterminantofimmunesystemandhepaticstellatecellbiologyopensnewperspectivestothemanagementofHIVinfectionanddisease...

【 授权许可】

CC BY