EGR1 regulates oral epithelial cell responses to Candida albicans via the EGFR- ERK1/2 pathway

Ruth E. Dickenson; Aize Pellon; Nicole O. Ponde; Olivia Hepworth; Lydia F. Daniels Gatward; Julian R. Naglik; David L. Moyes

doi:10.1080/21505594.2024.2435374

EGR1 regulates oral epithelial cell responses to Candida albicans via the EGFR- ERK1/2 pathway

Ruth E. Dickenson, Aize Pellon^*, Nicole O. Ponde, Olivia Hepworth, Lydia F. Daniels Gatward, Julian R. Naglik, David L. Moyes^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

88 Downloads (Pure)

Abstract

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.

Original language	English
Article number	2435374
Journal	Virulence
Volume	15
Issue number	1
Early online date	5 Dec 2024
DOIs	https://doi.org/10.1080/21505594.2024.2435374
Publication status	Published - 2024

Keywords

Candida albicans
Epithelial cells
EGR1

Access to Document

10.1080/21505594.2024.2435374Licence: CC BY

EGR1 regulates oral epithelial_DICKENSON_Publishedonline5December 2024_GOLD_VoR (CC BY)Final published version, 3.59 MBLicence: CC BY

Cite this

@article{dc38b97d3b824ff7b673af0a4c5a9e97,

title = "EGR1 regulates oral epithelial cell responses to Candida albicans via the EGFR- ERK1/2 pathway",

abstract = "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.",

keywords = "Candida albicans, Epithelial cells, EGR1",

author = "Dickenson, {Ruth E.} and Aize Pellon and Ponde, {Nicole O.} and Olivia Hepworth and {Daniels Gatward}, {Lydia F.} and Naglik, {Julian R.} and Moyes, {David L.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",

year = "2024",

doi = "10.1080/21505594.2024.2435374",

language = "English",

volume = "15",

journal = "Virulence",

issn = "2150-5594",

publisher = "Landes Bioscience",

number = "1",

}

TY - JOUR

T1 - EGR1 regulates oral epithelial cell responses to Candida albicans via the EGFR- ERK1/2 pathway

AU - Dickenson, Ruth E.

AU - Pellon, Aize

AU - Ponde, Nicole O.

AU - Hepworth, Olivia

AU - Daniels Gatward, Lydia F.

AU - Naglik, Julian R.

AU - Moyes, David L.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - Candida albicans

KW - Epithelial cells

KW - EGR1

UR - https://www.tandfonline.com/doi/full/10.1080/21505594.2024.2435374

UR - http://www.scopus.com/inward/record.url?scp=85211201791&partnerID=8YFLogxK

U2 - 10.1080/21505594.2024.2435374

DO - 10.1080/21505594.2024.2435374

M3 - Article

SN - 2150-5594

VL - 15

JO - Virulence

JF - Virulence

IS - 1

M1 - 2435374

ER -

EGR1 regulates oral epithelial cell responses to Candida albicans via the EGFR- ERK1/2 pathway

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this