Farnesol promotes epithelial cell defense against Candida albicans through Toll-like receptor 2 expression, interleukin-6 and human beta-defensin 2 production.
Farnesol, a quorum-sensing molecule, regulates virulence and morphogenesis in Candida albicans and is involved in various human pathologies including oral candidiasis. Oral epithelial cells are involved in innate immunity against Candida infections via Toll-like receptors (TLRs) and inflammatory mediators. We investigated the effects of farnesol on host cells and its possible synergistic interaction with gingival epithelial cells against C. albicans infection by studying the expression of TLR2, 4 and 6. The production of IL-6, IL-8, and human beta-defensins 1 and 2 was also examined using engineered human oral mucosa tissue put in contact with various concentrations of farnesol with and without C. albicans. Our findings indicate that 24 h after contact with C. albicans, epithelial cells expressed more TLR2 than did non-infected cells. The addition of exogenous farnesol upregulated the TLR2 expression by the gingival epithelial cells in the presence or absence of C. albicans. In contrast, TLR4 was down regulated when farnesol was added to the tissue with or without C. albicans. Finally, farnesol alone was shown to have no effect on TLR6, yet in the presence of both C. albicans and farnesol, TLR6 expression was down regulated. Farnesol modulated TLR2 expression by the epithelial cells following tissue contact with C. albicans. This effect was paralleled by IL-6 but not IL-8 secretion. Farnesol's effect on innate immunity was strengthened by its capacity to increase human beta-defensin 2 production, and by the efficacy of beta-defensin against C. albicans growth. Overall results showed that exogenous farnesol promoted epithelial cell defense against C. albicans infection through the involvement of TLR2, IL-6, and human beta-defensin 2.
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Groupe de Recherche en Ecologie Buccale, Faculté de Médecine Dentaire, Pavillon de Médecine Dentaire, Local 1728, 2420 rue de la Terrasse, Université Laval, Quebec, Que., Canada G1V 0A6.
Savignac
Katia
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Rouabhia
Mahmoud
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D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D002176:Candida albicans / Q000472:pathogenicity*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D005204:Farnesol / Q000494:pharmacology*; D005881:Gingiva / Q000166:cytology / Q000382:microbiology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D051216:Toll-Like Receptor 6 / Q000235:genetics / Q000378:metabolism; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*
D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; C406407:DEFB1 protein, human; C106641:DEFB4A protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D023083:beta-Defensins; D005204:Farnesol