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

<b>Objectives:</b> Oral candidiasis is commonly caused by <i>Candida albicans</i>, 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 <i>C. albicans</i> 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 <i>C. albicans</i> strains. <b>Methods:</b> 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 <i>C. albicans</i> strains, relationships of the amounts of those cytokines from oral keratinocytes with biofilm formation, phospholipase production, and <i>C. albicans</i> cytotoxicity were examined using Spearman correlation analysis. <b>Results:</b> Positive correlations of the amount of IL-8 with CXCL1 (<i>r</i>_s = 0.295, <i>p</i> = 0.0055) and IL-1β (<i>r</i>_s = 0.35, <i>p</i> = 0.0009) were noted, while a positive correlation was also found between amounts of GM-CSF and IL-8 (<i>r</i>_s = 0.306, <i>p</i> = 0.004), as well as IL-1β (<i>r</i>_s = 0.38, <i>p</i> = 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 (<i>r</i>_s = 0.736, <i>p</i> < 0.0001) and IL-8 (<i>r</i>_s = 0.371, <i>p</i> = 0.0004). <b>Conclusions:</b> The differential cytotoxicity of various <i>C. albicans</i> 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.