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.
Original language | English |
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Pages (from-to) | 20590-20599 |
Number of pages | 10 |
Journal | The Journal of Biological Chemistry |
Volume | 283 |
Issue number | 29 |
Early online date | 15 May 2008 |
DOIs | |
Publication status | Published - 18 Jul 2008 |
Keywords
- monocyte-derived macrophages
- toll-like receptors
- lectins DC-sign
- wall mannan
- serotype-B
- saccharomyces-cerevisiae
- surface hydrophobicity
- monoclonal-antibody
- pathogenic yeasts
- structural basis