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

Research output: Contribution to journalArticle

513 Citations (Scopus)

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

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

Fingerprint Dive into the research topics of 'Human dectin-1 deficiency and mucocutaneous fungal infections'. Together they form a unique fingerprint.

  • Cite this

    Ferwerda, B., Ferwerda, G., Plantinga, T. S., Willment, J. A., van Spriel, A. B., Venselaar, H., Elbers, C. C., Johnson, M. D., Cambi, A., Huysamen, C., Jacobs, L., Jansen, T., Verheijen, K., Masthoff, L., Morré, S. A., Vriend, G., Williams, D., Perfect, J. R., Joosten, L. A. B., ... 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