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

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‐γ (IFN‐γ). We show that IL‐13 and IL‐4 increase transcripts, total protein, and cell‐surface expression of DC‐SIGN in all MDM tested, IFN‐γ 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‐γ 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.