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EphA2 is an epithelial cell pattern recognition receptor for fungal β-glucans
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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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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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