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.
N1 - Publisher Copyright:
© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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 -