EGR1 regulates oral epithelial cell responses to Candida albicans via the EGFR- ERK1/2 pathway.
Ruth E DickensonAize PellonNicole O PondeOlivia HepworthLydia F Daniels GatwardJulian R NaglikDavid L MoyesPublished in: bioRxiv : the preprint server for biology (2023)
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.
Keyphrases
- candida albicans
- signaling pathway
- biofilm formation
- transcription factor
- small cell lung cancer
- epidermal growth factor receptor
- endothelial cells
- pi k akt
- cell proliferation
- tyrosine kinase
- poor prognosis
- healthcare
- oxidative stress
- dna binding
- escherichia coli
- ulcerative colitis
- induced pluripotent stem cells
- long non coding rna
- gene expression
- staphylococcus aureus
- lps induced
- nuclear factor
- pseudomonas aeruginosa