Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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Originally published online as doi:10.1189/jlb.0503231 on August 21, 2003

Published online before print August 21, 2003
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(Journal of Leukocyte Biology. 2003;74:757-763.)
© 2003 by Society for Leukocyte Biology

HIV-1 transmission and cytokine-induced expression of DC-SIGN in human monocyte-derived macrophages

Jihed Chehimi, Qi Luo, Livio Azzoni, Linda Shawver, Noel Ngoubilly, Ray June, Ghassen Jerandi, Matthew Farabaugh and Luis J. Montaner1

HIV Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, Pennsylvania

1 Correspondence: The Wistar Institute, 3601 Spruce Street, Room 480, Philadelphia, PA 19130. E-mail: montaner{at}wistar.upenn.edu

Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) has been described as an attachment molecule for human immunodeficiency virus type 1 (HIV-1) with the potential to mediate its transmission. We examined DC-SIGN expression in monocyte-derived macrophages (MDM) and its role in viral transmission when MDM were exposed to interleukin (IL)-13, IL-4, or interferon-{gamma} (IFN-{gamma}). We show that IL-13 and IL-4 increase transcripts, total protein, and cell-surface expression of DC-SIGN in all MDM tested, IFN-{gamma} results ranged from no change to up-regulation of surface expression, and message and total protein were, respectively, induced in all and 86% of donors tested. Transmission experiments of HIV-1 X4 between cytokine-treated MDM to Sup-T1 cells showed no association between total transmission and DC-SIGN up-regulation. IL-4 but not IL-13 resulted in a less than twofold increase in MDM viral transmission to CD4+ T cells in spite of a fourfold up-regulation in DC-SIGN expression by either cytokine. In contrast, IFN-{gamma} treatment induced a decrease in total transmission by at least two-thirds, despite its induction of DC-SIGN. Soluble mannan resulted in a greater inhibition of viral transmission to CD4+ T cells than neutralizing anti-DC-SIGN monoclonal antibody (67–75% vs. 39–48%), supporting the role of mannose-binding receptors in viral transmission. Taken together, results show that DC-SIGN regulation in MDM does not singly predict the transmission potential of this cell type.

Key Words: IL-4 • IL-13 • IFN-{gamma}




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