François Tardif, Jean Paul Goulet, Andrew Zakrzewski, Peter Chauvin, Mahmoud Rouabhia
Med Sci Monit 2004; 10(8): BR239-249
Background:Oral candidiasis is a collective name for a group of disorders caused by the dimorphic fungus Candida albicans (C. albicans). Host defenses against C. albicans essentially fall into two categories: specific immune mechanisms and local oral mucosal epithelial cell defenses. The rationale of this study was to investigate the involvement of IL-18 in the inflammatory response against oral candidiasis.Material/Methods: We first used human oral mucosa tissue and saliva to assess the production of Il-18. Second, we engineered human oral mucosa using only normal human oral epithelial cells and fibroblasts. Tissues were infected with C. albicans at different time points.Results: Tissue and saliva analyses demonstrated that constitutively produced and secreted IL-18 was up-regulated following Candida-infection. With our engineered model, we showed that C. albicans significantly increased the secretion of active IL-18 by infected epithelial cells. Interestingly, a significant secretion of IFNg functionally supported the up-regulation of active IL-18 in C. albicans-infected tissues. We also showed that rhIL-18 increased the expression and production of endogenous IL-18 and ICE in C. albicans-infected tissues, which was paralleled by a significant increase in IFNg secretion.Conclusions: These data suggest that (i) oral epithelial cells are involved in local host defenses against C. albicans infections, via IFNg induced-IL-18, and (ii) that IL-18 and IFNg secretions may be related to epithelial cells. Given that our experimental model closely mimics the natural interface between the oral mucosa and C. albicans, it appears that IL-18 meets the requirements of being a cytokine that epithelial cells use to control C. albicans infections.
Keywords: Candida albicans - metabolism, Candidiasis, Oral - immunology, Candidiasis, Oral - pathology, Coculture Techniques, Epithelial Cells - immunology, Epithelial Cells - microbiology, Epithelial Cells - pathology, Fibroblasts - metabolism, Fibroblasts - pathology, Humans, Interferon Type II - immunology, Interferon Type II - secretion, Interleukin-18 - immunology, Interleukin-18 - secretion, Mouth Mucosa - immunology, Mouth Mucosa - microbiology, Mouth Mucosa - pathology, Saliva - metabolism, Up-Regulation, Candida albicans - metabolism, Candidiasis, Oral - pathology, Coculture Techniques, Epithelial Cells - pathology, Fibroblasts - pathology, Humans, Interferon-gamma - secretion, Interleukin-18 - secretion, Mouth Mucosa - pathology, Saliva - metabolism, Up-Regulation