Dendritic Cell Interaction With Candida Albicans Critically Depends on N-Linked Mannan

Autor: 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.
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Zdroj: ETSU Faculty Works.
Druh dokumentu: Text
DOI: 10.1074/jbc.M709334200
Popis: 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.
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