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-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.
Chehimi
Jihed
J
HIV Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, PA, USA.
Luo
Qi
Q
Azzoni
Livio
L
Shawver
Linda
L
Ngoubilly
Noel
N
June
Ray
R
Jerandi
Ghassen
G
Farabaugh
Matthew
M
Montaner
Luis J
LJ
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000635:transmission*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000235:genetics*; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D037181:Lectins, C-Type / Q000187:drug effects / Q000235:genetics*; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics*; D015854:Up-Regulation; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D016207:Cytokines; D007371:Interferon-gamma; D018793:Interleukin-13; D015847:Interleukin-4; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin