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Journal of Virology, February 2002, p. 1866-1875, Vol. 76, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.4.1866-1875.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Brian Jameson,1 Frédéric Baribaud,2 Stefan Pöhlmann,2 Darlene Ghavimi,2 Frank Mortari,3 Robert W. Doms,2 and Akiko Iwasaki4*

Department of Pathology,1 Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520,4 Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104,2 R&D Systems, Minneapolis, Minnesota 554133

Received 17 September 2001/ Accepted 13 November 2001

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.

* Corresponding author. Mailing address: Department of Epidemiology and Public Health, 60 College St., LEPH 716, New Haven, CT 06510. Phone: (203) 785-2919. Fax: (203) 785-7552. E-mail: akiko.iwasaki{at}yale.edu.

Journal of Virology, February 2002, p. 1866-1875, Vol. 76, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.4.1866-1875.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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