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- Title
Langerin is a natural barrier to HIV-1 transmission by Langerhans cells.
- Authors
de Witte, Lot; Nabatov, Alexey; Pion, Marjorie; Fluitsma, Donna; de Jong, Marein A W P; de Gruijl, Tanja; Piguet, Vincent; van Kooyk, Yvette; Geijtenbeek, Teunis B H
- Abstract
Human immunodeficiency virus-1 (HIV-1) is primarily transmitted sexually. Dendritic cells (DCs) in the subepithelium transmit HIV-1 to T cells through the C-type lectin DC-specific intercellular adhesion molecule (ICAM)-3-grabbing nonintegrin (DC-SIGN). However, the epithelial Langerhans cells (LCs) are the first DC subset to encounter HIV-1. It has generally been assumed that LCs mediate the transmission of HIV-1 to T cells through the C-type lectin Langerin, similarly to transmission by DC-SIGN on dendritic cells (DCs). Here we show that in stark contrast to DC-SIGN, Langerin prevents HIV-1 transmission by LCs. HIV-1 captured by Langerin was internalized into Birbeck granules and degraded. Langerin inhibited LC infection and this mechanism kept LCs refractory to HIV-1 transmission; inhibition of Langerin allowed LC infection and subsequent HIV-1 transmission. Notably, LCs also inhibited T-cell infection by viral clearance through Langerin. Thus Langerin is a natural barrier to HIV-1 infection, and strategies to combat infection must enhance, preserve or, at the very least, not interfere with Langerin expression and function.
- Publication
Nature medicine, 2007, Vol 13, Issue 3, p367
- ISSN
1078-8956
- Publication type
Journal Article
- DOI
10.1038/nm1541