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

Abstract:

: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.

journal_name

J Leukoc Biol

authors

Chehimi J,Luo Q,Azzoni L,Shawver L,Ngoubilly N,June R,Jerandi G,Farabaugh M,Montaner LJ

doi

10.1189/jlb.0503231

subject

Has Abstract

pub_date

2003-11-01 00:00:00

pages

757-63

issue

5

eissn

0741-5400

issn

1938-3673

pii

jlb.0503231

journal_volume

74

pub_type

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