Relationship Between Virulence Factor Activities, Cytotoxicity of Candida albicans Strains Isolated from Oral Cavity, and Cytokine Production by Oral Keratinocytes Exposed to Those Strains.

Objectives: Oral candidiasis is commonly caused by Candida albicans, which possesses virulence factors and shows cytotoxic activity that affects oral keratinocytes. On the other hand, oral keratinocytes are known to induce immune responses against C. albicans infection. The aim of the present study was to investigate the relationships of various cytokines produced from oral keratinocytes with virulence factor activities and cytotoxicity of C. albicans strains. Methods: Following the determination of the amounts of cytokines (IL-1β, IL-8, TNF-α, CCL20, CXCL1, GM-CSF) produced by oral keratinocytes when exposed to 87 different C. albicans strains, relationships of the amounts of those cytokines from oral keratinocytes with biofilm formation, phospholipase production, and C. albicans cytotoxicity were examined using Spearman correlation analysis. Results: Positive correlations of the amount of IL-8 with CXCL1 (rs = 0.295, p = 0.0055) and IL-1β (rs = 0.35, p = 0.0009) were noted, while a positive correlation was also found between amounts of GM-CSF and IL-8 (rs = 0.306, p = 0.004), as well as IL-1β (rs = 0.38, p = 0.0003). In contrast, there were no significant correlations among biofilm formation, phospholipase production, or amounts of various cytokines produced by oral keratinocytes. Furthermore, a positive correlation was noted between cytotoxicity to oral keratinocytes and amounts of IL-1β (rs = 0.736, p < 0.0001) and IL-8 (rs = 0.371, p = 0.0004). Conclusions: The differential cytotoxicity of various C. albicans strains has an influence on the production of specific cytokines from oral keratinocytes. Additionally, cytokines produced by oral keratinocytes may be mutually involved with similar signaling activation and/or autocrine/paracrine functions.