Langerin is a natural barrier to HIV-1 transmission by Langerhans cells.
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.
de Witte
Lot
L
Department of Molecular Cell Biology and Immunology, VU University Medical Center, van de Boechorstraat 7, 1081BT Amsterdam, The Netherlands.
Nabatov
Alexey
A
Pion
Marjorie
M
Fluitsma
Donna
D
de Jong
Marein A W P
MA
de Gruijl
Tanja
T
Piguet
Vincent
V
van Kooyk
Yvette
Y
Geijtenbeek
Teunis B H
TB
D000818:Animals; D019380:Anti-HIV Agents / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D037181:Lectins, C-Type / Q000378:metabolism / Q000502:physiology*; D037241:Mannose-Binding Lectins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding / Q000276:immunology
D019380:Anti-HIV Agents; D015703:Antigens, CD; C121916:CD207 protein, human; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins