Farnesol modulates TLRs and mediators expression following C. albicans

Farnesol, a quorum sensing molecule, regulates virulence and morphogenesis in C. albicans. This yeast is involved in different human pathologies including oral candidiasis. Oral epithelial cells are involved in innate immunity against Candida infections via Toll-like receptors (TLRs) and inflammatory mediators. Objectives: The purpose of this study was to investigate the effects of farnesol on C. albicans modulation of TLR2, 4 and 6 expressions, and IL-6 and IL-8 productions by oral mucosa tissue. Methods: Engineered human oral mucosa tissue was produced using oral epithelial cells and fibroblasts. Tissues were put in contact with farnesol (10, 100 and 300 µg/ml) with and without C. albicans (10³/cm²) and maintained in culture for 4 and 24 h. Epithelia were used to investigate TLR2, 4 and 6 genes expression using quantitative RT-PCR. Culture supernatants were used to investigate IL-6, IL-8 and human ß-defensin productions. Results: We showed that, 24 h after infection epithelial cells express more TLR2 following contact with C. albicans. The addition exogenous farnesol up-regulated TLR2 expression as compared to those tissues infected with C. albicans only. The addition of farnesol down-regulated the expression of TLR4 at 4 h but increased it at 24h. C. albicans infection reduced TLR4 expression only after 4 h. The presence of farnesol down-regulated TLR4 expression following C. albicans infection only at 4 h. No effect on TLR6 was observed. The effect of farnesol and C. albicans on TLR 2 and 4 expressions was paralleled by IL-6 and IL-8 increase when tissue was stimulated with farnesol/C. albicans infection. The inflammatory response was strengthening by human ß-defensin-2 production. Conclusion: All together, these results showed that epithelial cells prevent C. albicans infection through TLRs. The presence of exogenous farnesol promotes epithelial cell defence against C. albicans infection. (This study was funded by NSERC-CIHR ).