Human dectin-1 deficiency and mucocutaneous fungal infections

Bart Ferwerda, Gerben Ferwerda, Theo S Plantinga, Janet A Willment, Annemiek B van Spriel, Hanka Venselaar, Clara C Elbers, Melissa D. Johnson, Alessandra Cambi, Cristal Huysamen, Liesbeth Jacobs, Trees Jansen, Karlijn Verheijen, Laury Masthoff, Servaas A Morré, Gert Vriend, David Williams, John R Perfect, Leo A B Joosten, Cisca WijmengaJos W M van der Meer, Gosse J Adema, Bart Jan Kullberg, Gordon D Brown, Mihai G Netea

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Abstract

Mucocutaneous fungal infections are typically found in patients who have no known immune defects. We describe a family in which four women who were affected by either recurrent vulvovaginal candidiasis or onychomycosis had the early-stop-codon mutation Tyr238X in the beta-glucan receptor dectin-1. The mutated form of dectin-1 was poorly expressed, did not mediate beta-glucan binding, and led to defective production of cytokines (interleukin-17, tumor necrosis factor, and interleukin-6) after stimulation with beta-glucan or Candida albicans. In contrast, fungal phagocytosis and fungal killing were normal in the patients, explaining why dectin-1 deficiency was not associated with invasive fungal infections and highlighting the specific role of dectin-1 in human mucosal antifungal defense.
Original languageEnglish
Pages (from-to)1760-1767
Number of pages8
JournalThe New England Journal of Medicine
Volume361
Issue number18
DOIs
Publication statusPublished - 29 Oct 2009

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Keywords

  • animals
  • Candida albicans
  • candidiasis
  • candidiasis, chronic mucocutaneous
  • candidiasis, vulvovaginal
  • codon, nonsense
  • cytokines
  • female
  • genetic predisposition to disease
  • humans
  • male
  • mammals
  • membrane proteins
  • nerve tissue proteins
  • onychomycosis
  • pedigree

Cite this

Ferwerda, B., Ferwerda, G., Plantinga, T. S., Willment, J. A., van Spriel, A. B., Venselaar, H., ... Netea, M. G. (2009). Human dectin-1 deficiency and mucocutaneous fungal infections. The New England Journal of Medicine, 361(18), 1760-1767. https://doi.org/10.1056/NEJMoa0901053