Nature Medicine, Volume 13: Pages 367-371, 4 March 2007.
¹ Department of Molecular Cell Biology and Immunology, VU University Medical Center, van de Boechorstraat 7, 1081BT Amsterdam, The Netherlands.
² Department of Dermatology and Venereology, University Hospital of Geneva, 24 Rue Micheli-du-Crest, 1211 Geneva, Switzerland.
³ Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
Correspondence should be addressed to T.G. ( t.geijtenbeek@vumc.nl).
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.
Received 13 October 2006; accepted 21 December 2006; published online 4 March 2007; doi:10.1038/nm1541
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