The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
EphA2 is an epithelial cell pattern recognition receptor for fungal β-glucans
Open accessPublished version of a preprint
Abstract
Oral epithelial cells discriminate between pathogenic and non-pathogenic stimuli, and only induce an inflammatory response when they are exposed to high levels of a potentially harmful microorganism. The pattern recognition receptors (PRRs) in epithelial cells that mediate this differential response are poorly understood. Here, we demonstrate that the ephrin type-A receptor 2 (EphA2) is an oral epithelial cell PRR that binds to exposed β-glucans on the surface of the fungal pathogen Candida albicans. Binding of C. albicans to EphA2 on oral epithelial cells activates signal transducer and activator of transcription 3 and mitogen-activated protein kinase signalling in an inoculum-dependent manner, and is required for induction of a proinflammatory and antifungal response. EphA2 -/- mice have impaired inflammatory responses and reduced interleukin-17 signalling during oropharyngeal candidiasis, resulting in more severe disease. Our study reveals that EphA2 functions as a PRR for β-glucans that senses epithelial cell fungal burden and is required for the maximal mucosal inflammatory response to C. albicans.
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“A recent study has shown C. glabrata to induce phosphorylation of the ephrin type-A receptor 2 (EphA2), that binds to β-glucan, in immortalized normal human oral keratinocytes (OKF6/TERT-2) [136].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [136]
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“Collectively, these results indicate that EphA2 signaling is necessary for a maximal IL-17 response during OPC.”
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Aberrant type 1 immunity drives susceptibility to mucosal fungal infections.
Break, T. J., Oikonomou, V., Dutzan, N., Desai, J. V., Swidergall, M., Freiwald, T., Chauss, D., Harrison, O. J., Alejo, J., Williams, D. W., et al. (2021) · Science · doi:10.1126/science.aay5731 · Cited by 175
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Metadata
- Authors
- Swidergall, M., Solis, N. V., Lionakis, M. S., & Filler, S. G.
- Affiliations
- The Lundquist Institute (US)
- National Institutes of Health (US)
- University of California, Los Angeles (US)
- Corresponding author
- Filler, Scott G.
- Venue
- Nature Microbiology
- Published
- 2017-11-13
- Volume
- 3
- Issue
- 1
- Pages
- 53-61
- ISSN
- 2058-5276 (ISSN-L)
- PMC
- PMC5736406
- OpenAlex
- W2949823271
- Cited by
- 167
- References
- 47
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 17 · 2023: 14 · 2022: 24 · 2021: 26 · 2020: 25 · 2019: 17 · 2018: 18 · 2017: 1
- FWCI
- 12.84
- Type
- journal article
- Language
- en
- Update notices
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Microbiology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI124566)
- National Institute of Dental and Craniofacial Research (K99DE026856, R01DE026600)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- EphA2, pattern recognition receptors, β-glucan, Candida albicans, oral epithelial cells, oropharyngeal candidiasis, STAT3 signaling, MAPK signaling, IL-17, mucosal inflammation, innate immunity
- MeSH terms
- Animals, Candida albicans, Candidiasis, Oral, Cell Line, Disease Models, Animal, Endocytosis, Epithelial Cells, Male, Mice, Inbred C57BL, Mouth Mucosa, Phosphorylation, Signal Transduction, Cytokines, Inflammation Mediators, Receptor, EphA2, beta-Glucans, STAT3 Transcription Factor, Receptors, Pattern Recognition, Mice, ErbB Receptors
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