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

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...

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Bibliographic Details
Published in:The Journal of biological chemistry 2008-07, Vol.283 (29), p.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: Article
Language:English
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
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M709334200