Human dectin-1 deficiency and mucocutaneous fungal infections
Open accessAbstract
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.
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The Y238X Dectin-1 polymorphism associated with increased fungal risk is overrepresented in some populations and may be responsible for the increased risk for fungal diseases observed in certain demographic groups.
“The Y238X Dectin-1 polymorphism associated with increased fungal risk is overrepresented in some populations [16] and may be responsible for the increased risk for fungal diseases observed in certain demographic groups.”
From Race and ethnicity: Risk factors for fungal infections? (2023) · cites this paper as [16]
Numerous single-nucleotide polymorphisms within human Toll-like receptors and C-type lectin receptors have been identified as risk factors for fungal disease.
“Numerous single-nucleotide polymorphisms (SNPs) within human TLRs (TLR1 [11], TLR4 [12–15], TLR6 [11], among others) and CLRs (Dectin-1—in particular the Y238X SNP [16–18]; DC-SIGN, mannose receptor and mannose-binding lectin [19–22]) have been identified as risk factors for fungal disease.”
From Race and ethnicity: Risk factors for fungal infections? (2023) · cites this paper as [16]
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Self-citation
- Authors
- 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. L., Perfect, J. R., Joosten, L. A. B., Wijmenga, C., van der Meer, J. W. M., Adema, G. J., Kullberg, B. J., Brown, G. D., & Netea, M. G.
- Affiliations
- Radboud University Nijmegen (NL)
- University of Cape Town (ZA)
- University Medical Center Utrecht (NL)
- Duke University (US)
- Vrije Universiteit Amsterdam (NL)
- East Tennessee State University (US)
- University Medical Center Groningen (NL)
- ORCID
- Ferwerda, Bart
- Ferwerda, Gerben
- Plantinga, Theo S.
- Willment, Janet A.
- Venselaar, Hanka
- Elbers, Clara C.
- Johnson, Melissa D.
- Cambi, Alessandra
- Masthoff, Laury
- Morré, Servaas A.
- Vriend, Gert
- Williams, David L.
- Perfect, John R.
- Joosten, Leo A.B.
- Wijmenga, Cisca
- Adema, Gosse J.
- Kullberg, Bart Jan
- Brown, Gordon D.
- Netea, Mihai G.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2009-10-29
- Volume
- 361
- Issue
- 18
- Pages
- 1760-1767
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC2773015
- OpenAlex
- W2101524137
- Cited by
- 752
- References
- 32
- Citations by year
- 2026: 15 · 2025: 18 · 2024: 31 · 2023: 15 · 2022: 31 · 2021: 36 · 2020: 37 · 2019: 32 · 2018: 33 · 2017: 48 · 2016: 61 · 2015: 51 · 2014: 64 · 2013: 56 · 2012: 72
- FWCI
- 31.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- PubMed Central (acceptedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Digital Commons - East Tennessee State University (East Tennessee State University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Abbott Laboratories
- Pfizer
- Wellcome Trust (068545/Z/02), 086558, G0000934, 068545)
- KWF Kankerbestrijding (2007-3917)
- Astellas Pharma
- Basilea Pharmaceutica
- Medical Research Council (068545/Z/02, G0000934)
- National Institute of Allergy and Infectious Diseases (K23AI051537, L30 AI057128)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- mucocutaneous fungal infections, beta-glucan receptor, recurrent vulvovaginal candidiasis, onychomycosis, Candida albicans, cytokine production, IL-17, TNF-α, interleukin-6, inherited immunodeficiency
- MeSH terms
- Dectin-1, Animals, Candida albicans, Candidiasis, Candidiasis, Chronic Mucocutaneous, Candidiasis, Vulvovaginal, Female, Humans, Male, Mammals, Membrane Proteins, Nerve Tissue Proteins, Pedigree, Onychomycosis, Cytokines, Codon, Nonsense, Genetic Predisposition to Disease, Lectins, C-Type
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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