title: Mutz-3-derived Langerhans cells are a model to study HIV-1 transmission and potential inhibitors.
abstract: 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.
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands 1105AZ.
authors.forename: Marein A W P
authors.initials: MA
authors.lastname: de Jong
authors.forename: Lot
authors.initials: L
authors.lastname: de Witte
authors.forename: Saskia J A M
authors.initials: SJ
authors.lastname: Santegoets
authors.forename: Donna
authors.initials: D
authors.lastname: Fluitsma
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Taylor
authors.forename: Tanja D
authors.initials: TD
authors.lastname: de Gruijl
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
mesh_terms: D019380:Anti-HIV Agents; D015703:Antigens, CD / Q000096:biosynthesis; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D007801:Langerhans Cells / Q000378:metabolism / Q000821:virology*; D037181:Lectins, C-Type / Q000096:biosynthesis; D037241:Mannose-Binding Lectins / Q000096:biosynthesis; D008954:Models, Biological; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD; C121916:CD207 protein, human; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins