Dendritic cell interaction with Candida albicans critically depends on N-linked mannan

Alessandra Cambi, Mihai G. Netea, Hector M. Mora-Montes, Neil A. R. Gow, Stanleyson V. Hato, Douglas W. Lowman, Bart-Jan Kullberg, Ruurd Torensma, David L. Williams, Carl G. Figdor

Research output: Contribution to journalArticle

138 Citations (Scopus)

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 languageEnglish
Pages (from-to)20590-20599
Number of pages10
JournalThe Journal of Biological Chemistry
Volume283
Issue number29
Early online date15 May 2008
DOIs
Publication statusPublished - 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

Cite this

Cambi, A., Netea, M. G., Mora-Montes, H. M., Gow, N. A. R., Hato, S. V., Lowman, D. W., ... Figdor, C. G. (2008). Dendritic cell interaction with Candida albicans critically depends on N-linked mannan. The Journal of Biological Chemistry, 283(29), 20590-20599. https://doi.org/10.1074/jbc.M709334200

Dendritic cell interaction with Candida albicans critically depends on N-linked mannan. / 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.

In: The Journal of Biological Chemistry, Vol. 283, No. 29, 18.07.2008, p. 20590-20599.

Research output: Contribution to journalArticle

Cambi, A, Netea, MG, Mora-Montes, HM, Gow, NAR, Hato, SV, Lowman, DW, Kullberg, B-J, Torensma, R, Williams, DL & Figdor, CG 2008, 'Dendritic cell interaction with Candida albicans critically depends on N-linked mannan', The Journal of Biological Chemistry, vol. 283, no. 29, pp. 20590-20599. https://doi.org/10.1074/jbc.M709334200
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. / Dendritic cell interaction with Candida albicans critically depends on N-linked mannan. In: The Journal of Biological Chemistry. 2008 ; Vol. 283, No. 29. pp. 20590-20599.
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