Dendritic cells express multiple chemokine receptors used as coreceptors for HIV entry.
Cells of the dendritic lineage are thought to be among the first cells infected after mucosal exposure to HIV. In this study, we have identified the presence of multiple chemokine receptors on dendritic cells (DC) that may function as coreceptors for HIV entry. DC effectively used CCR5 for entry of macrophage (M)-tropic isolates. CCR3, the eotaxin receptor, initially identified on eosinophils, is expressed on DC and may be used as an entry coreceptor by certain dual-tropic strains. CXCR4 was not expressed on DC, although SDF-1 induced a calcium flux and DC could be infected by T cell line (T)-tropic HIV. Our findings provide evidence for the presence of a non-CXCR4 SDF-1 receptor on DC that is used mainly by T-tropic strains of HIV. DC from individuals homozygous for a 32-bp deletion of the CCR5 gene are also infectable with M-tropic strains of HIV-1, and this infection is inhibited by stromal cell-derived factor (SDF)1, suggesting that this receptor can also be used by M-tropic HIV for entry. Delineation of the spectrum of coreceptor usage on DC may offer new approaches to interfere with the initiation and propagation of HIV infection.
Rubbert
A
A
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1576, USA.
Combadiere
C
C
Ostrowski
M
M
Arthos
J
J
Dybul
M
M
Machado
E
E
Cohn
M A
MA
Hoxie
J A
JA
Murphy
P M
PM
Fauci
A S
AS
Weissman
D
D
D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D054377:Chemokine CXCL12; D018925:Chemokines / Q000494:pharmacology; D019743:Chemokines, CXC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D017931:DNA Primers / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D015870:Gene Expression; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054389:Receptors, CCR1; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics* / Q000502:physiology; D015728:Receptors, HIV / Q000235:genetics* / Q000502:physiology
C515300:CCR1 protein, human; C515350:CCR3 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D017931:DNA Primers; D012333:RNA, Messenger; D054389:Receptors, CCR1; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D015728:Receptors, HIV; D002118:Calcium