Early Stop Polymorphism in Human DECTIN‐1 Is Associated with Increased Candida Colonization in Hematopoietic Stem Cell Transplant Recipients
Open accessAbstract
Background. Intensive treatment of hematological malignancies with hematopoietic stem cell transplantation (HSCT) is accompanied by a high incidence of opportunistic invasive fungal infection, but individual risk varies significantly. Dectin-1, a C-type lectin that recognizes 1,3-beta-glucans from fungal pathogens, including Candida species, is involved in the initiation of the immune response against fungi. Methods. Screening for the DECTIN-1 Y238X polymorphism within a group of 142 patients undergoing HSCT was correlated with Candida colonization and candidemia. Furthermore, functional studies were performed on the consequences of the polymorphism. Results. Patients bearing the Y238X polymorphism in the DECTIN-1 gene were more likely to be colonized with Candida species, compared with patients bearing wild-type DECTIN-1, necessitating more frequent use of fluconazole in the prevention of systemic Candida infection. Functional assays demonstrated a loss-of-function phenotype of the polymorphism, as shown by the decreased cytokine production by immune cells bearing this polymorphism. Conclusions. The Y238X polymorphism is associated with increased oral and gastrointestinal colonization with Candida species. This suggests a crucial role played by dectin-1 in the mucosal antifungal mechanisms in immunocompromised hosts. The finding that DECTIN-1 polymorphisms rendered HSCT recipients at increased risk for fungal complications may contribute to the selection of high-risk patients who should be considered for antifungal prophylaxis to prevent systemic candidiasis.
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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 [18]
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- Authors
- Plantinga, T. S., van der Velden, W. J. F. M., Ferwerda, B., van Spriel, A. B., Adema, G., Feuth, T., Donnelly, J. P., Brown, G. D., Kullberg, B., Blijlevens, N. M. A., & Netea, M. G.
- Affiliations
- Radboud University Nijmegen (NL)
- University of Cape Town (ZA)
- Corresponding author
- Netea, Mihai G.
- ORCID
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-09
- Volume
- 49
- Issue
- 5
- Pages
- 724-732
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- OpenAlex
- W2150753599
- Cited by
- 247
- References
- 24
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 8 · 2023: 6 · 2022: 10 · 2021: 15 · 2020: 11 · 2019: 7 · 2018: 11 · 2017: 11 · 2016: 16 · 2015: 25 · 2014: 22 · 2013: 16 · 2012: 27
- FWCI
- 19.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Dectin-1, Candida colonization, hematopoietic stem cell transplantation, candidemia, C-type lectin, loss-of-function polymorphism, cytokine production, fluconazole prophylaxis, immunocompromised patients, fungal infection risk
- MeSH terms
- Dectin-1, Adolescent, Adult, Aged, Antifungal Agents, Candida, Candidiasis, Female, Humans, Male, Membrane Proteins, Middle Aged, Nerve Tissue Proteins, Opportunistic Infections, Polymorphism, Genetic, Retrospective Studies, Fluconazole, Immunocompromised Host, Hematopoietic Stem Cell Transplantation, Lectins, C-Type, Young Adult
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