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EGR1 regulates oral epithelial cell responses to Candida albicans via the EGFR- ERK1/2 pathway
Candida albicans is a fungal pathobiont colonising 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....
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10103955/ https://www.ncbi.nlm.nih.gov/pubmed/37066428 http://dx.doi.org/10.1101/2023.03.31.535186 |
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author | Dickenson, Ruth E. Pellon, Aize Ponde, Nicole O. Hepworth, Olivia Daniels Gatward, Lydia F. Naglik, Julian R. Moyes, David L. |
author_facet | Dickenson, Ruth E. Pellon, Aize Ponde, Nicole O. Hepworth, Olivia Daniels Gatward, Lydia F. Naglik, Julian R. Moyes, David L. |
author_sort | Dickenson, Ruth E. |
collection | PubMed |
description | Candida albicans is a fungal pathobiont colonising 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 colonisation 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 | Online Article Text |
id | pubmed-10103955 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-101039552023-04-15 EGR1 regulates oral epithelial cell responses to Candida albicans via the EGFR- ERK1/2 pathway Dickenson, Ruth E. Pellon, Aize Ponde, Nicole O. Hepworth, Olivia Daniels Gatward, Lydia F. Naglik, Julian R. Moyes, David L. bioRxiv Article Candida albicans is a fungal pathobiont colonising 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 colonisation 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. Cold Spring Harbor Laboratory 2023-04-03 /pmc/articles/PMC10103955/ /pubmed/37066428 http://dx.doi.org/10.1101/2023.03.31.535186 Text en https://creativecommons.org/licenses/by-nc/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Dickenson, Ruth E. Pellon, Aize Ponde, Nicole O. Hepworth, Olivia Daniels Gatward, Lydia F. Naglik, Julian R. Moyes, David L. EGR1 regulates oral epithelial cell responses to Candida albicans via the EGFR- ERK1/2 pathway |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10103955/ https://www.ncbi.nlm.nih.gov/pubmed/37066428 http://dx.doi.org/10.1101/2023.03.31.535186 |
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