The C-type lectin DC-SIGN internalizes soluble antigens and HIV-1 virions via a clathrin-dependent mechanism.
Dendritic cells (DC), professional Ag-presenting cells located in mucosae and lymphoid organs, operate at the interface of innate and adaptive immunity and are likely the first cells to encounter invading HIV-1. Although the C-type lectin DC-Specific ICAM-3-grabbing non-integrin (DC-SIGN) binds to several viruses, including HIV-1, its direct involvement in viral entry remains controversial. Despite its central role in DC function, little is known about the underlying molecular mechanism(s) of DC-SIGN-mediated Ag uptake. Here, we analyzed the early stages of DC-SIGN-mediated endocytosis and demonstrate that both membrane cholesterol and dynamin are required. Confocal microscopy and clathrin RNAi showed that DC-SIGN-mediated internalization occurs via clathrin-coated pits. Electron microscopy of ultrathin sections showed the involvement of DC-SIGN in clathrin-dependent HIV-1 internalization by DC. Currently, DC-specific C-type lectins are considered potential target in anti-tumor clinical trials. Detailed information about how different Ag are internalized via these receptors will facilitate the rational design of targeted therapeutic strategies.
Cambi
Alessandra
A
Department of Tumor Immunology, Radboud University Nijmegen Medical Centre, The Netherlands.
Beeren
Inge
I
Joosten
Ben
B
Fransen
Jack A
JA
Figdor
Carl G
CG
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D002966:Clathrin / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D034741:RNA, Small Interfering / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012995:Solubility; D014162:Transfection; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000941:Antigens; D015815:Cell Adhesion Molecules; D002784:Cholesterol; D002966:Clathrin; D034281:Dynamins; D037181:Lectins, C-Type; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin