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

Journal of Leukocyte Biology

Linda Shawver¹  Livio Azzoni¹  Qi Luo¹  Ray June¹  Ghassen Jerandi¹  Jihed Chehimi¹  Luis J. Montaner¹  Matthew Farabaugh¹  Noel Ngoubilly¹ 

[1] HIV Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, PennsylvaniaHIV Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, PennsylvaniaHIV Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, Pennsylvania

关键词: IL-4;    IL-13;    IFN-γ;   

DOI  :  10.1189/jlb.0503231

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown