Mutz-3-derived Langerhans cells are a model to study HIV-1 transmission and potential inhibitors
Mutz-3-derived Langerhans cells are a model to study HIV-1 transmission and potential inhibitors
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DOI：
10.1189/jlb.0809577
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发表时间：
2010-04-01
影响因子：
5.5
通讯作者：
Geijtenbeek, Teunis B. H.
中科院分区：
文献类型：
--
作者：
de Jong, Marein A. W. P.;de Witte, Lot;Geijtenbeek, Teunis B. H.
性传播是HIV-1感染的主要途径，DC亚群被认为参与了病毒向T细胞的传播。在生殖器粘膜中，存在两个主要的DC亚群：上皮型LCS通过C型凝集素Langerin捕获和降解HIV-1，而上皮下型DCs表达DC-SIGN，促进HIV-1向T细胞传播。由于目前没有艾滋病毒-1疫苗可用，杀微生物剂提供了一种替代战略来限制艾滋病毒-1的传播。然而，LCS的低利用率和供体差异阻碍了对LCS功能的研究。在这里，我们开始研究来自MUTZ-3细胞系(Mu-LCS)的LCS是否为研究LCS在HIV-1传播中的作用和寻找合适的潜在杀菌剂提供了一个有价值的工具。我们证明了Mu-LCS的表型类似于人类原代LCS；Mu-LCS不能有效地传播HIV-1，抑制Langerin可以增强HIV-1向T细胞的传播。我们表明，阻止DC-SIGN而不是Langerin的碳水化合物结构是潜在的杀菌剂，因为它们阻止了DC传播HIV-1，但不影响LCS的抗病毒功能。因此，Mu-LCS是研究LCS在HIV-1传播中的作用和筛选潜在杀菌剂的合适模型。J.Leukoc。比奥尔。87：637-643；2010。
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. J. Leukoc. Biol. 87: 637-643; 2010.