title: Regulated recruitment of DC-SIGN to cell-cell contact regions during zymosan-induced human dendritic cell aggregation.
abstract: Zymosan is a beta-glucan, mannan-rich yeast particle widely used to activate the inflammatory response of immune cells. We studied the zymosan-binding potential of human dendritic cells (hDCs) by using specific carbohydrate inhibitors and blocking monoclonal antibodies. We show that DC-specific intercellular adhesion molecule-grabbing nonintegrin (DC-SIGN) is a major nonopsonic recognition receptor for zymosan on hDCs. Indeed, blocking of DC-SIGN inhibited the inflammatory response of DCs to zymosan. We compared the zymosan-binding capacity of hDC-SIGN to that of Dectin-1 and complement receptor 3 (CR3), which are receptors involved in the nonopsonic recognition of these yeast-derived particles. Dectin-1- and DC-SIGN-K562 cells bound to zymosan particles, whereas CR3-K562 cells did not. DC-SIGN and Dectin-1 were also expressed in COS cells to compare their ability to trigger particle internalization in a nonphagocytic cell line. DC-SIGN transfectants were unable to internalize bound particles, indicating that DC-SIGN is primarily involved in recognition but not in particle internalization. Zymosan induced a rapid DC aggregation that was accompanied by a dramatic change of DC-SIGN distribution in the plasma membrane. Under resting conditions, DC-SIGN was diffusely distributed through the cell surface, displaying clusters at the free leading edge. Upon zymosan treatment, DC-SIGN was markedly redistributed to cell-cell contacts, supporting an adhesion role in DC-DC interactions. The mechanism(s) supporting DC-SIGN-mediated intercellular adhesion were further investigated by using DC-SIGN-K562 aggregation. DC-SIGN was highly concentrated at points of cell-cell contact, suggesting a role for enhanced avidity during DC-SIGN-mediated intercellular adhesion.
authors.affiliation: Servicio de Inmunología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: de la Rosa
authors.forename: María
authors.initials: M
authors.lastname: Yáñez-Mó
authors.forename: Raphael
authors.initials: R
authors.lastname: Samaneigo
authors.forename: Diego
authors.initials: D
authors.lastname: Serrano-Gómez
authors.forename: Laura
authors.initials: L
authors.lastname: Martínez-Muñoz
authors.forename: Elena
authors.initials: E
authors.lastname: Fernández-Ruiz
authors.forename: Natividad
authors.initials: N
authors.lastname: Longo
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.forename: Angel L
authors.initials: AL
authors.lastname: Corbí
authors.forename: Paloma
authors.initials: P
authors.lastname: Sánchez-Mateos
mesh_terms: D000818:Animals; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002449:Cell Aggregation / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D006801:Humans; D020014:K562 Cells; D037181:Lectins, C-Type / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D009000:Monocytes / Q000276:immunology / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D015003:Yeasts / Q000276:immunology; D015054:Zymosan / Q000276:immunology / Q000494:pharmacology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000099181:Dectin-1
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D016177:Macrophage-1 Antigen; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D015054:Zymosan; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000099181:Dectin-1