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Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells

2004; Rockefeller University Press; Volume: 164; Issue: 1 Linguagem: Inglês

10.1083/jcb.200306112

1540-8140

Alessandra Cambi, Frank de Lange, Noortje M. van Maarseveen, Monique Nijhuis, Ben Joosten, E.M.H.P. van Dijk, B.I. de Bakker, Jack Fransen, Petra H. M. Bovée‐Geurts, Frank N. van Leeuwen, N.F. van Hulst, Carl G. Figdor,

Immune Response and Inflammation

The C-type lectin dendritic cell (DC)–specific intercellular adhesion molecule grabbing non-integrin (DC-SIGN; CD209) facilitates binding and internalization of several viruses, including HIV-1, on DCs, but the underlying mechanism for being such an efficient phagocytic pathogen-recognition receptor is poorly understood. By high resolution electron microscopy, we demonstrate a direct relation between DC-SIGN function as viral receptor and its microlocalization on the plasma membrane. During development of human monocyte-derived DCs, DC-SIGN becomes organized in well-defined microdomains, with an average diameter of 200 nm. Biochemical experiments and confocal microscopy indicate that DC-SIGN microdomains reside within lipid rafts. Finally, we show that the organization of DC-SIGN in microdomains on the plasma membrane is important for binding and internalization of virus particles, suggesting that these multimolecular assemblies of DC-SIGN act as a docking site for pathogens like HIV-1 to invade the host.