Dendritic Cell Interaction with Candida albicans Critically Depends on N-Linked Mannan

• Published in: The Journal of biological chemistry Vol. 283; no. 29; pp. 20590 - 20599
• Main Authors: Cambi, Alessandra, Netea, Mihai G., Mora-Montes, Hector M., Gow, Neil A.R., Hato, Stanleyson V., Lowman, Douglas W., Kullberg, Bart-Jan, Torensma, Ruurd, Williams, David L., Figdor, Carl G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.07.2008; American Society for Biochemistry and Molecular Biology
• Subjects: Candida albicans - immunology; Cell Adhesion Molecules - immunology; Cells, Cultured; Cytokines - biosynthesis; Dendritic Cells - immunology; Glycosylation; Humans; Lectins, C-Type - immunology; Mannans - chemistry; Mannans - immunology; Molecular Structure; Phagocytes - immunology; Protein Binding; Receptors, Cell Surface - immunology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M709334200

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.