Mutz-3-derived Langerhans cells are a model to study HIV-1 transmission and potential inhibitors

被引:23
作者
de Jong, Marein A. W. P. [1 ,2 ]
de Witte, Lot [4 ]
Santegoets, Saskia J. A. M. [3 ]
Fluitsma, Donna [2 ]
Taylor, Maureen E. [5 ]
de Gruijl, Tanja D. [3 ]
Geijtenbeek, Teunis B. H. [1 ]
机构
[1] Univ Amsterdam, Acad Med Ctr, Ctr Expt & Mol Med, NL-1105 AZ Amsterdam, Netherlands
[2] Vrije Univ Amsterdam, Med Ctr, Dept Mol Cell Biol & Immunol, Amsterdam, Netherlands
[3] Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, Amsterdam, Netherlands
[4] Univ Med Ctr, Erasmus MC, Dept Virol, Rotterdam, Netherlands
[5] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, Div Mol Biosci, London, England
基金
英国惠康基金;
关键词
dendritic cells; Langerin; microbicides; HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN GP120; BINDS DC-SIGN; C-TYPE LECTIN; DENDRITIC CELLS; T-CELLS; BIRBECK GRANULES; DIFFERENTIATION; INFECTION; RECEPTOR;
D O I
10.1189/jlb.0809577
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:637 / 643
页数:7
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