We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Candidalysin activates innate epithelial immune responses via epidermal growth factor receptor.
- Authors
Jemima Ho; Xuexin Yang; Nikou, Spyridoula-Angeliki; Kichik, Nessim; Donkin, Andrew; Ponde, Nicole O.; Richardson, Jonathan P.; Gratacap, Remi L.; Archambault, Linda S.; Zwirner, Christian P.; Murciano, Celia; Henley-Smith, Rhonda; Thavaraj, Selvam; Tynan, Christopher J.; Gaffen, Sarah L.; Hube, Bernhard; Wheeler, Robert T.; Moyes, David L.; Naglik, Julian R.
- Abstract
Candida albicans is a fungal pathobiont, able to cause epithelial cell damage and immune activation. These functions have been attributed to its secreted toxin, candidalysin, though the molecular mechanisms are poorly understood. Here, we identify epidermal growth factor receptor (EGFR) as a critical component of candidalysin-triggered immune responses. We find that both C. albicans and candidalysin activate human epithelial EGFR receptors and candidalysin-deficient fungal mutants poorly induce EGFR phosphorylation during murine oropharyngeal candidiasis. Furthermore, inhibition of EGFR impairs candidalysin-triggered MAPK signalling and release of neutrophil activating chemokines in vitro, and diminishes neutrophil recruitment, causing significant mortality in an EGFR-inhibited zebrafish swim-bladder model of infection. Investigation into the mechanism of EGFR activation revealed the requirement of matrix metalloproteinases (MMPs), EGFR ligands and calcium. We thus identify a PAMP-independent mechanism of immune stimulation and highlight candidalysin and EGFR signalling components as potential targets for prophylactic and therapeutic intervention of mucosal candidiasis.
- Publication
Nature Communications, 2019, Vol 10, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-019-09915-2