title: Role of DC-SIGN in the activation of dendritic cells by HPV-16 L1 virus-like particle vaccine.
abstract: Dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN), a specific C-type lectin expressed on DC, binds and transmits different pathogens to susceptible cells. In the present study, we examined the role of DC-SIGN in the capture of human papillomavirus (HPV) pseudovirions and activation of DC. We demonstrate that HPV virus-like particles (VLP) bind to DC-SIGN expressed on transfected Raji cells and that antibodies against DC-SIGN block this interaction. DC take up VLP, which activate expression of costimulatory markers and cytokines/chemokines. Although our results indicate that DC-SIGN is not the major receptor for VLP in DC, this interaction contributes to the activation of DC surface antigens (HLA class I) and of various cytokines/chemokines, particularly TNF-alpha, IL-6, and RANTES. Induction of these markers in DC by VLP was significantly abrogated when binding to DC-SIGN was blocked by anti-DC-SIGN antibodies. These results suggest that DC-SIGN has a functional role in DC activation induced by HPV-16 L1-VLP, and thus highlight new aspects of DC interactions with HPV VLP.
authors.affiliation: SAIC-Frederick/NCI-Frederick, Frederick, MD, USA.
authors.forename: Alfonso J
authors.initials: AJ
authors.lastname: García-Piñeres
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Matthew
authors.initials: M
authors.lastname: Trivett
authors.forename: Marcus
authors.initials: M
authors.lastname: Williams
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Vineet N
authors.initials: VN
authors.lastname: Kewalramani
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D053918:Papillomavirus Vaccines; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D014765:Viral Vaccines / Q000276:immunology*; D014771:Virion / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016207:Cytokines; D037181:Lectins, C-Type; D053918:Papillomavirus Vaccines; D011956:Receptors, Cell Surface; D014765:Viral Vaccines; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin