title: Expression of DC-SIGN by dendritic cells of intestinal and genital mucosae in humans and rhesus macaques.
abstract: To better understand the role of dendritic cells (DCs) in human immunodeficiency virus (HIV) transmission at mucosal surfaces, we examined the expressions of the HIV adhesion molecule, dendritic-cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN), its closely related homologue DC-SIGNR, and HIV coreceptors by distinct DC populations in the intestinal and genital tracts of humans and rhesus macaques. We also developed monoclonal antibodies (MAbs) specific for DC-SIGN or DC-SIGNR. In the Peyer's patches, DC-SIGN expression was detected in the interfollicular regions and in clusters 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 contained cells that expressed high levels of DC-SIGN throughout the entire thickness of the mucosa, while solitary lymphoid nodules within the rectum showed very little staining for DC-SIGN. Triple-color analysis of rectal tissue indicated that CCR5(+) CD4(+) DC-SIGN(+) DCs were localized just beneath the luminal epithelium. These findings suggest that DC-SIGN(+) DCs could play a role in the transmission of primate lentiviruses in the ileum and the rectum whereas accessibility to DC-SIGN(+) cells is limited in an intact vaginal mucosa. Finally, we identified a MAb that blocked simian immunodeficiency virus interactions with rhesus macaque DC-SIGN. This and other specific MAbs may be used to assess the relevance of DC-SIGN in virus transmission in vivo.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Jameson
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baribaud
authors.forename: Stefan
authors.initials: S
authors.lastname: Pöhlmann
authors.forename: Darlene
authors.initials: D
authors.lastname: Ghavimi
authors.forename: Frank
authors.initials: F
authors.lastname: Mortari
authors.forename: Robert W
authors.initials: RW
authors.lastname: Doms
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwasaki
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D015815:Cell Adhesion Molecules; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D037102:Lectins / Q000276:immunology / Q000378:metabolism*; D037181:Lectins, C-Type; D008253:Macaca mulatta; D051379:Mice; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology*; D010581:Peyer's Patches / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D012007:Rectum / Q000166:cytology / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control / Q000635:transmission; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D014621:Vagina / Q000166:cytology / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D037102:Lectins; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human