AEGiS-9CROI: Expression of DC-SIGN by Intestinal and Genital Mucosal Dendritic Cells in Humans and Rhesus Macaques

9th Conference on Retroviruses and Opportunistic Infections


Seattle, Washington - February 24 -February 28, 2002

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Expression of DC-SIGN by Intestinal and Genital Mucosal Dendritic Cells in Humans and Rhesus Macaques

Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 28
Jameson B, Baribaud F, Pohlmann S, Ghavimi D, Mortari F, Doms R, Iwasaki A; Yale Univ., New Haven, CT

BACKGROUND: Dendritic cells (DCs) are proposed to play a key role in HIV transmission and pathogenesis. To better understand the mechanism of HIV interaction with DCs at mucosal surfaces, we examined the expression of the HIV adhesion molecule, dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN), its closely related homologue DC-SIGNR, and HIV co-receptors by distinct DC populations in the intestinal and genital tracts of humans and rhesus macaques using monoclonal antibodies specific for either DC-SIGN or DC-SIGNR.

METHODS: Monoclonal antibodies to DC-SIGN or DC-SIGNR were generated in mice immunized with 3T3 cells expressing human DC-SIGN or DC-SIGNR and screened for specificity and their ability to inhibit virus adhesion. Frozen sections of human and rhesus macaque intestinal and genital tissues were stained with antibodies to DC-SIGN, DC-SIGNR, or various DC markers and visualized by immunofluorescence microscopy and confocal microscopy.

RESULTS: In the Peyer's patches, DC-SIGN expression was detected in the interfollicular regions as well as in a cluster of cells in the subepithelial dome regions. DC-SIGN expression was not found on plasmacytoid DCs. DC-SIGNR expression was restricted to endothelial cells in approximately one-third of the capillaries in the terminal ileum. In the vaginal epithelium, Langerhans' cells did not express DC-SIGN, whereas subepithelial DCs in the lamina propria expressed moderate levels of DC-SIGN. Finally, the rectum was found to contain cells that express high levels of DC-SIGN throughout the entire thickness of the mucosa. Triple color analysis of rectal tissue indicated that CCR5+/CD4+/DC-SIGN+ DCs were localized just beneath the luminal epithelium.

CONCLUSIONS: These findings suggest that DC-SIGN+ DCs could play a role in transmission of primate lentiviruses in the ileum and the rectum whereas accessibility to DC-SIGN+ cells is limited in an intact vaginal mucosa.

Keywords: Cell Adhesion Molecules, Dendritic Cells, Receptors, Cell Surface, Macaca mulatta, Lectins, C-Type, Mucous Membrane, Receptors, HIV, Hominidae, HIV Infections, Endothelium, Antigens, CD4, Antibodies, Monoclonal, Peyer's Patches, Greece, DC-SIGNR protein, human, DC-specific ICAM-3 grabbing nonintegrin, Human, Animal, Mice, Female, immunology

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Copyright © 2002 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.