Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands 1105AZ.
J Leukoc Biol. 2010 Apr;87(4):637-43. doi: 10.1189/jlb.0809577. Epub 2009 Dec 30.
Sexual transmission is the primary route of HIV-1 infection, and DC subsets are thought to be involved in viral dissemination to T cells. In the genital mucosa, two main subsets of DCs are present: epithelial LCs capture and degrade HIV-1 through C-type lectin Langerin, whereas subepithelial DCs express DC-SIGN, which facilitates HIV-1 transmission to T cells. As there is currently no HIV-1 vaccine available, microbicides provide an alternative strategy to limit HIV-1 spread. However, research into the function of LCs is hampered by the low availability and donor differences. Here, we set out to investigate whether LCs derived from the Mutz-3 cell line (Mu-LCs) provide a valuable tool to investigate the role of LCs in HIV-1 transmission and identify suitable potential microbicides. We demonstrate that Mu-LCs phenotypically resemble human primary LCs; Mu-LCs do not transmit HIV-1 efficiently, and inhibition of Langerin enhances HIV-1 transmission to T cells. We show that carbohydrate structures blocking DC-SIGN but not Langerin are potential microbicides, as they prevent HIV-1 transmission by DCs but do not affect the antiviral function of LCs. Therefore, Mu-LCs are a suitable model to investigate the role of LCs in HIV-1 transmission and to screen potential microbicides.
性传播是 HIV-1 感染的主要途径，人们认为树突状细胞亚群参与了病毒向 T 细胞的传播。在生殖道黏膜中，存在两种主要的树突状细胞亚群：上皮细胞中的 LC 通过 C 型凝集素 langerin 捕获和降解 HIV-1，而黏膜下的树突状细胞表达 DC-SIGN，这有利于 HIV-1 向 T 细胞的传播。由于目前尚无 HIV-1 疫苗，杀微生物剂提供了一种限制 HIV-1 传播的替代策略。然而，由于 LC 的可用性低和供体差异，对 LC 功能的研究受到了阻碍。在这里，我们着手研究 Mutz-3 细胞系（Mu-LC）衍生的 LC 是否为研究 LC 在 HIV-1 传播中的作用以及鉴定合适的潜在杀微生物剂提供了有价值的工具。我们证明 Mu-LC 在表型上类似于人原代 LC；Mu-LC 不能有效地传播 HIV-1，并且抑制 langerin 增强了 HIV-1 向 T 细胞的传播。我们表明，阻断 DC-SIGN 但不阻断 langerin 的碳水化合物结构是潜在的杀微生物剂，因为它们通过树突状细胞阻止 HIV-1 的传播，但不影响 LC 的抗病毒功能。因此，Mu-LC 是研究 LC 在 HIV-1 传播中的作用和筛选潜在杀微生物剂的合适模型。
