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 β-glucan receptor dectin-1. The mutated form of dectin-1 was poorly expressed, did not mediate β-glucan binding, and led to defective production of cytokines (interleukin-17, tumor necrosis factor, and interleukin-6) after stimulation with β-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.
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From the Department of Internal Medicine and the Nijmegen Institute for Infection, Inflammation, and Immunity (B.F., G.F., T.S.P., L.J., T.J., K.V., L.M., L.A.B.J., J.W.M.M., B.J.K., M.G.N.); the Department of Tumor Immunology and the Nijmegen Center for Molecular Life Sciences (A.B.S., A.C., G.J.A.); and the Center for Molecular and Biomolecular Informatics, Nijmegen Center for Molecular Life Sciences (H.V., G.V.) — all at Radboud University Nijmegen, Nijmegen; the Complex Genetics Section, Department of Medical Genetics, Division of Biomedical Genetics (C.C.E., C.W.), and the Julius Center for Health Sciences and Primary Care (C.C.E.), University Medical Center Utrecht, Utrecht; the Laboratory of Immunogenetics, Vrije Universiteit, Amsterdam (S.A.M.); and the Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen (C.W.) — all in the Netherlands; the Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa (J.A.W., C.H., G.D.B.); the Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, NC (M.D.J., J.R.P.); and the Department of Surgery, East Tennessee State University, Johnson City (D.L.W.).
Drs. B. Ferwerda and G. Ferwerda contributed equally to this article.
Address reprint requests to Dr. Netea at the Department of Medicine (463), Radboud University, Nijmegen Medical Center, Geert Grooteplein 8, 6525GA Nijmegen, the Netherlands, or at m.netea{at}aig.umcn.nl.
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