Langerin is a natural barrier to HIV-1 transmission by Langerhans cells

Lot de Witte, Alexey Nabatov, Marjorie Pion, Donna Fluitsma, Marein A W P de Jong, Tanja de Gruijl, Vincent Piguet, Yvette van Kooyk, Teunis B H Geijtenbeek

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)367-71
Number of pages5
JournalNature Medicine
Volume13
Issue number3
DOIs
Publication statusPublished - Mar 2007

Cite this