Expression and function of CCR5 and CXCR4 on human Langerhans cells and macrophages: implications for HIV primary infection.
Transmission of HIV-1 is predominantly restricted to macrophage (Mphi)-tropic strains. Langerhans cells (LCs) in mucosal epithelium, as well as macrophages located in the submucosal tissues, may be initial targets for HIV-1. This study was designed to determine whether restricted transmission of HIV-1 correlates with expression and function of HIV-1 co-receptors on LCs and macrophages. Using polyclonal rabbit IgGs specific for the HIV co-receptors cytokines CXCR4 and CCR5, we found that freshly isolated epidermal LCs (resembling resident mucosal LCs) expressed CCR5, but not CXCR, on their surfaces. In concordance with surface expression, fresh LCs fused with Mphi-tropic but not with T-tropic HIV-1 envelopes. However, fresh LCs did contain intracellular CXCR4 protein that was transported to the surface during in vitro culture. Macrophages expressed high levels of both co-receptors on their surfaces, but only CCR5 was functional in a fusion assay. These data provide several possible explanations for the selective transmission of Mphi-tropic HIV variants and for the resistance to infection conferred by the CCR5 deletion.
Zaitseva
M
M
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Blauvelt
A
A
Lee
S
S
Lapham
C K
CK
Klaus-Kovtun
V
V
Mostowski
H
H
Manischewitz
J
J
Golding
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity; D002459:Cell Fusion; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007801:Langerhans Cells / Q000378:metabolism / Q000821:virology*; D008264:Macrophages / Q000378:metabolism / Q000821:virology*; D008969:Molecular Sequence Data; D011817:Rabbits; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000276:immunology; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000276:immunology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D019713:Receptors, CCR5; D019718:Receptors, CXCR4