Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans
Open accessAbstract
Candida albicans is the most common human fungal pathogen causing mucosal and systemic infections. However, human antifungal immunity remains poorly defined. Here by integrating transcriptional analysis and functional genomics, we identified Candida-specific host defence mechanisms in humans. Candida induced significant expression of genes from the type I interferon pathway in human peripheral blood mononuclear cells. This unexpectedly prominent role of type I interferon pathway in anti-Candida host defence was supported by additional evidence. Polymorphisms in type I interferon genes modulated Candida-induced cytokine production and were correlated with susceptibility to systemic candidiasis. In in vitro experiments, type I interferons skewed Candida-induced inflammation from a Th17 response towards a Th1 response. Patients with chronic mucocutaneous candidiasis displayed defective expression of genes in the type I interferon pathway. These findings indicate that the type I interferon pathway is a main signature of Candida-induced inflammation and has a crucial role in anti-Candida host defence in humans.
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The TII response is also induced by bacterial, parasitic, and fungal infections.
“this response is also induced by bacterial, parasitic (43), and fungal infections (30, 44 – 48).”
From Overlooked <i>Candida glabrata</i> petites are echinocandin tolerant, induce host inflammatory responses, and display poor <i>in vivo</i> fitness (2023) · cites this paper as [47]
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- Authors
- Smeekens, S. P., Ng, A., Kumar, V., Johnson, M. D., Plantinga, T. S., van Diemen, C., Arts, P., Verwiel, E. T. P., Gresnigt, M. S., Fransen, K., van Sommeren, S., Oosting, M., Cheng, S.-C., Joosten, L. A. B., Hoischen, A., Kullberg, B.-J., Scott, W. K., Perfect, J. R., van der Meer, J. W. M., Wijmenga, C., Netea, M. G., & Xavier, R. J.
- Affiliations
- Radboud University Medical Center (NL)
- Broad Institute (US)
- University Medical Center Groningen (NL)
- Campbell University (US)
- Radboud University Nijmegen (NL)
- University of Miami (US)
- Corresponding author
- Netea, Mihai G.
- ORCID
- Venue
- Nature Communications
- Published
- 2013-01-08
- Volume
- 4
- Issue
- 1
- Pages
- 1342-1342
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC3625375
- OpenAlex
- W2083051190
- Cited by
- 213
- References
- 46
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 15 · 2023: 10 · 2022: 19 · 2021: 14 · 2020: 16 · 2019: 7 · 2018: 15 · 2017: 20 · 2016: 21 · 2015: 10 · 2014: 39 · 2013: 7 · 2012: 1
- FWCI
- 18.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Funders
- Leona M. and Harry B. Helmsley Charitable Trust (DK043351)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (918.66.620)
- National Institutes of Health (DK 043351)
- National Institute of Allergy and Infectious Diseases (AI 062773, R01AI062773)
- National Institute of Diabetes and Digestive and Kidney Diseases ((DK043351, R01DK083756, DK 83756, R01DK064869, P30DK043351)
- FP7 Ideas: European Research Council (310372)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- Candida albicans, type I interferon pathway, antifungal immunity, host defense against fungi, systemic candidiasis, chronic mucocutaneous candidiasis, peripheral blood mononuclear cells, cytokine production, Th17 response, Th1 response, genetic polymorphism, inflammation
- MeSH terms
- Candida albicans, Candidiasis, Chronic Mucocutaneous, Gene Expression Regulation, Humans, Interferon Type I, Mutation, Transcription, Genetic, Signal Transduction, Cluster Analysis, Case-Control Studies, Th1 Cells, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genomics, STAT1 Transcription Factor, Host-Pathogen Interactions, Candidemia, Th17 Cells
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