IADR Abstract Archives
Epithelial activation by the novel fungal peptide toxin Candidalysin
Objectives: The human fungal pathogen Candida albicans causes millions of mucosal (oral, vaginal) and life-threatening systemic (blood) infections each year. Efforts to understand how C. albicans causes disease have remained at the forefront of medical mycology for several decades. Our recent discovery of Candidalysin, the first cytolytic peptide toxin identified in any human fungal pathogen, finally revealed how C. albicans activates oral epithelial cells (via the mitogen-activated protein kinase (MAPK) pathway), induces tissue damage (by forming pores) and promotes infections in a murine oral model. Given that the vast majority of Candida infections are vaginal, this study aimed to extend our oral studies and determine the importance of Candidalysin in activating vaginal epithelial cells.
Methods: Epithelial monolayer cultures of the A431 human vulvar epidermoid carcinoma cell line were inoculated with C. albicans Candidalysin at a range of concentrations between 5 – 250 μg/ml. Epithelial cell lysates were assayed for MAPK pathway activation (via activation of the MAPK phosphatase (MKP-1) and the transcription factor c-Fos), the production of cytokines (GM-CSF, G-CSF, IL-1α, IL-1β, IL-6, and IL-8), and the induction of cell damage (via lactate dehydrogenase (LDH) release). Data were analysed by one-way ANOVA.
Results: Candidalysin was found to activate MKP-1/c-Fos and induce cytokines and cell damage in vaginal epithelial cells in a dose-dependent manner, with increasing concentrations of Candidalysin being more stimulatory. Similar findings were observed previously in oral epithelial cells.
Conclusions: These data indicate that the core epithelial response to Candidalysin is conserved between oral and vaginal epithelium and provides valuable new insights in our understanding of host epithelial responses to the medically important fungus Candida albicans.
Methods: Epithelial monolayer cultures of the A431 human vulvar epidermoid carcinoma cell line were inoculated with C. albicans Candidalysin at a range of concentrations between 5 – 250 μg/ml. Epithelial cell lysates were assayed for MAPK pathway activation (via activation of the MAPK phosphatase (MKP-1) and the transcription factor c-Fos), the production of cytokines (GM-CSF, G-CSF, IL-1α, IL-1β, IL-6, and IL-8), and the induction of cell damage (via lactate dehydrogenase (LDH) release). Data were analysed by one-way ANOVA.
Results: Candidalysin was found to activate MKP-1/c-Fos and induce cytokines and cell damage in vaginal epithelial cells in a dose-dependent manner, with increasing concentrations of Candidalysin being more stimulatory. Similar findings were observed previously in oral epithelial cells.
Conclusions: These data indicate that the core epithelial response to Candidalysin is conserved between oral and vaginal epithelium and provides valuable new insights in our understanding of host epithelial responses to the medically important fungus Candida albicans.