EGR1 regulates oral epithelial cell responses to Candida albicans via the EGFR- ERK1/2 pathway
Candida albicans is a fungal pathobiont colonizing mucosal surfaces of the human body, including the oral cavity. Under certain predisposing conditions, C. albicans invades mucosal tissues activating EGFR-MAPK signalling pathways in epithelial cells via the action of its peptide toxin candidalysin....
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Virulence |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21505594.2024.2435374 |
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| author | Ruth E. Dickenson Aize Pellon Nicole O. Ponde Olivia Hepworth Lydia F. Daniels Gatward Julian R. Naglik David L. Moyes |
| author_facet | Ruth E. Dickenson Aize Pellon Nicole O. Ponde Olivia Hepworth Lydia F. Daniels Gatward Julian R. Naglik David L. Moyes |
| author_sort | Ruth E. Dickenson |
| collection | DOAJ |
| description | Candida albicans is a fungal pathobiont colonizing mucosal surfaces of the human body, including the oral cavity. Under certain predisposing conditions, C. albicans invades mucosal tissues activating EGFR-MAPK signalling pathways in epithelial cells via the action of its peptide toxin candidalysin. However, our knowledge of the epithelial mechanisms involved during C. albicans colonization is rudimentary. Here, we describe the role of the transcription factor early growth response protein 1 (EGR1) in human oral epithelial cells (OECs) in response to C. albicans. EGR1 expression increases in OECs when exposed to C. albicans independently of fungal viability, morphology, or candidalysin release, suggesting EGR1 is involved in the fundamental recognition of C. albicans, rather than in response to invasion or “pathogenesis.” Upregulation of EGR1 is mediated by EGFR via Raf1, ERK1/2, and NF-κB signalling but not PI3K/mTOR signalling. Notably, EGR1 mRNA silencing impacts on anti-C. albicans immunity, reducing GM-CSF, IL-1α and IL-1β release, and increasing IL-6 and IL-8 production. These findings identify an important role for EGR1 in priming epithelial cells to respond to subsequent invasive infection by C. albicans and elucidate the regulation circuit of this transcription factor after contact. |
| format | Article |
| id | doaj-art-e6b8f9a9f7084d768ebf6555876e0ee2 |
| institution | Kabale University |
| issn | 2150-5594 2150-5608 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj-art-e6b8f9a9f7084d768ebf6555876e0ee22024-12-05T10:48:39ZengTaylor & Francis GroupVirulence2150-55942150-56082024-12-0115110.1080/21505594.2024.2435374EGR1 regulates oral epithelial cell responses to Candida albicans via the EGFR- ERK1/2 pathwayRuth E. Dickenson0Aize Pellon1Nicole O. Ponde2Olivia Hepworth3Lydia F. Daniels Gatward4Julian R. Naglik5David L. Moyes6Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, UKCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, UKCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, UKCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, UKCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, UKCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, UKCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, UKCandida albicans is a fungal pathobiont colonizing mucosal surfaces of the human body, including the oral cavity. Under certain predisposing conditions, C. albicans invades mucosal tissues activating EGFR-MAPK signalling pathways in epithelial cells via the action of its peptide toxin candidalysin. However, our knowledge of the epithelial mechanisms involved during C. albicans colonization is rudimentary. Here, we describe the role of the transcription factor early growth response protein 1 (EGR1) in human oral epithelial cells (OECs) in response to C. albicans. EGR1 expression increases in OECs when exposed to C. albicans independently of fungal viability, morphology, or candidalysin release, suggesting EGR1 is involved in the fundamental recognition of C. albicans, rather than in response to invasion or “pathogenesis.” Upregulation of EGR1 is mediated by EGFR via Raf1, ERK1/2, and NF-κB signalling but not PI3K/mTOR signalling. Notably, EGR1 mRNA silencing impacts on anti-C. albicans immunity, reducing GM-CSF, IL-1α and IL-1β release, and increasing IL-6 and IL-8 production. These findings identify an important role for EGR1 in priming epithelial cells to respond to subsequent invasive infection by C. albicans and elucidate the regulation circuit of this transcription factor after contact.https://www.tandfonline.com/doi/10.1080/21505594.2024.2435374EGR1Candidaepithelial cell |
| spellingShingle | Ruth E. Dickenson Aize Pellon Nicole O. Ponde Olivia Hepworth Lydia F. Daniels Gatward Julian R. Naglik David L. Moyes EGR1 regulates oral epithelial cell responses to Candida albicans via the EGFR- ERK1/2 pathway Virulence EGR1 Candida epithelial cell |
| title | EGR1 regulates oral epithelial cell responses to Candida albicans via the EGFR- ERK1/2 pathway |
| title_full | EGR1 regulates oral epithelial cell responses to Candida albicans via the EGFR- ERK1/2 pathway |
| title_fullStr | EGR1 regulates oral epithelial cell responses to Candida albicans via the EGFR- ERK1/2 pathway |
| title_full_unstemmed | EGR1 regulates oral epithelial cell responses to Candida albicans via the EGFR- ERK1/2 pathway |
| title_short | EGR1 regulates oral epithelial cell responses to Candida albicans via the EGFR- ERK1/2 pathway |
| title_sort | egr1 regulates oral epithelial cell responses to candida albicans via the egfr erk1 2 pathway |
| topic | EGR1 Candida epithelial cell |
| url | https://www.tandfonline.com/doi/10.1080/21505594.2024.2435374 |
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