Involvement of interleukin-18 in the inflammatory response against oropharyngeal candidiasis François Tardif 1 BDE, Jean-Paul Goulet 1 BCDFG, Andrew Zakrzewski 1 BCDF, Peter Chauvin 2 BCDF, Mahmoud Rouabhia 1 ACDEFG 1 Faculté de médicine dentaire et Groupe de recherche en écologie buccale, Pavillon de médecine dentaire, Université Laval, Québec City, Canada 2 Faculty of Dentistry, McGill University, Montréal, Québec, Canada Source of support: This work was supported by grants from the Natural Sciences and Engineering Research Council (Contract grant number: 227212-99), the Canadian Institutes of Health Research (Contract grant number: MOP-12591) and the Fonds de la Recherche en Santé du Québec (Contract grant number: 015006.01). Mahmoud Rouabhia is a senior research scholar of the FRSQ program. Summary 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 en- gineered 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-re- gulated following Candida-infection. With our engineered model, we showed that C. albicans signifi- cantly 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 se- cretion. 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 epi- thelial 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. key words: oral candidiasis • Candida albicans • oral mucosa • IL-18 • IFNg • tissue engineering Full-text PDF: http://www.MedSciMonit.com/pub/vol_10/no_8/4477.pdf Word count: 4975 Tables: 2 Figures: 9 References: 43 Author’s address: Dr. Mahmoud Rouabhia, Faculté de médecine dentaire, Pavillon de médecine dentaire, Local 1728, Université Laval, Québec, G1K 7P4, Canada. e-mail: Mahmoud.rouabhia@fmd.ulaval.ca Authors’ Contribution: A Study Design B Data Collection C Statistical Analysis D Data Interpretation E Manuscript Preparation F Literature Search G Funds Collection Received: 2003.12.23 Accepted: 2004.02.11 Published: 2004.08.01 BR239 Basic Research WWW. MED S CI MONIT .COM © Med Sci Monit, 2004; 10(8): BR239-249 PMID: 15277983 BR