HIV-1 transmission and cytokine-induced expression of DC-SIGN in human monocyte-derived macrophages
HIV-1 transmission and cytokine-induced expression of DC-SIGN in human monocyte-derived macrophages
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DOI：
10.1189/jlb.0503231
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发表时间：
2003-11-01
影响因子：
5.5
通讯作者：
Montaner, LJ
中科院分区：
文献类型：
--
作者：
Chehimi, J;Luo, Q;Montaner, LJ
树突状细胞特异性细胞间粘附分子-3-抓取非整合素（DC-SIGN）已被描述为人类免疫缺陷病毒1型（HIV-1）的附着分子，具有介导其传播的潜力。我们研究了DC-SIGN在单核细胞衍生的巨噬细胞（MDM）中的表达及其在MDM暴露于白细胞介素（IL）-13，IL-4或干扰素-γ（IFN-γ）时在病毒传播中的作用。我们发现，IL-13和IL-4增加转录本，总蛋白，DC-SIGN的细胞表面表达在所有的MDM测试，IFN-γ的结果范围从没有变化到上调的表面表达，和消息和总蛋白，分别诱导在所有和86%的捐助者测试。HIV-1 X4在经奎宁处理的MDM与Sup-T1细胞之间的传播实验显示，总传播与DC-SIGN上调之间没有关联。IL-4而不是IL-13导致MDAI病毒向CD 4（+）T细胞的传播增加不到两倍，尽管两种细胞因子均可使DC-SIGN表达上调4倍。相反，IFN-γ治疗诱导总传输减少至少三分之二，尽管其诱导DC-SIGN。可溶性甘露聚糖对病毒传播至CD 4（+）T细胞的抑制作用比中和抗DC-SIGN单克隆抗体更大（67-75% vs. 39-48%）。支持甘露糖结合受体在病毒传播中的作用。总之，结果表明，MDM中的DC-SIGN调节并不能单独预测这种细胞类型的传播潜力。J. Leukoc. 74：757-763; 2003.
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 MDAI 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. J. Leukoc. Biol. 74: 757-763; 2003.