title: Dendritic cell interaction with Candida albicans critically depends on N-linked mannan.
abstract: The fungus Candida albicans is the most common cause of mycotic infections in immunocompromised hosts. Little is known about the initial interactions between Candida and immune cell receptors, because a detailed characterization at the structural level is lacking. Antigen-presenting dendritic cells (DCs), strategically located at mucosal surfaces and in the skin, may play an important role in anti-Candida protective immunity. However, the contribution of the various Candida-associated molecular patterns and their counter-receptors to DC function remains unknown. Here, we demonstrate that two C-type lectins, DC-SIGN and the macrophage mannose receptor, specifically mediate C. albicans binding and internalization by human DCs. Moreover, by combining a range of C. albicans glycosylation mutants with receptor-specific blocking and cytokine production assays, we determined that N-linked mannan but not O-linked or phosphomannan is the fungal carbohydrate structure specifically recognized by both C-type lectins on human DCs and directly influences the production of the proinflammatory cytokine IL-6. Better insight in the carbohydrate recognition profile of C-type lectins will ultimately provide relevant information for the development of new drugs targeting specific fungal cell wall antigens.
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cambi
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Hector M
authors.initials: HM
authors.lastname: Mora-Montes
authors.forename: Neil A R
authors.initials: NA
authors.lastname: Gow
authors.forename: Stanleyson V
authors.initials: SV
authors.lastname: Hato
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Lowman
authors.forename: Bart-Jan
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: Ruurd
authors.initials: R
authors.lastname: Torensma
authors.forename: David L
authors.initials: DL
authors.lastname: Williams
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
mesh_terms: D002176:Candida albicans / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D006031:Glycosylation; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology; D008351:Mannans / Q000737:chemistry / Q000276:immunology*; D015394:Molecular Structure; D010586:Phagocytes / Q000276:immunology; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000276:immunology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D037181:Lectins, C-Type; D008351:Mannans; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin