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. 2007 Mar;13(3):367-71.
doi: 10.1038/nm1541. Epub 2007 Mar 4.

Langerin Is a Natural Barrier to HIV-1 Transmission by Langerhans Cells

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Langerin Is a Natural Barrier to HIV-1 Transmission by Langerhans Cells

Lot de Witte et al. Nat Med. .

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.

Comment in

  • Langerhans cells lap up HIV-1.
    Schwartz O. Schwartz O. Nat Med. 2007 Mar;13(3):245-6. doi: 10.1038/nm0307-245. Nat Med. 2007. PMID: 17342114 No abstract available.

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