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

hesion molecule-3-grabbing nonintegrin (DC-SIGN) has been described as an attachment mole-cule for human immunodeficiency virus type 1 (HIV-1) with the potential to mediate its transmis-sion. We examined DC-SIGN expression in mono-cyte-derived macrophages (MDM) and its role in viral transmission when MDM were exposed to in-terleukin (IL)-13, IL-4, or interferon- (IFN-). We show that IL-13 and IL-4 increase transcripts, total protein, and cell-surface expression of DC-SIGN in all MDM tested, IFN- 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. Trans-mission experiments of HIV-1 X4 between cyto-kine-treated MDM to Sup-T1 cells showed no asso-ciation 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 con-trast, IFN- treatment induced a decrease in total transmission by at least two-thirds, despite its in-duction 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 trans-mission. Taken together, results show that DC-SIGN regulation in MDM does not singly predict the transmission potential of this cell type. J. Leu-koc. Biol. 74: 757–763; 2003