Involvement of interleukin-18 in the inflammatory response against oropharyngeal candidiasis.
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.


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.
Tardif
François
F
Faculté de médicine dentaire et Groupe de recherche en écologie buccale, Pavillon de médecine dentaire, Université Laval, Québec City, Canada.
Goulet
Jean-Paul
JP
Zakrazewski
Andrew
A
Chauvin
Peter
P
Rouabhia
Mahmoud
M
D002176:Candida albicans / Q000378:metabolism; D002180:Candidiasis, Oral / Q000276:immunology* / Q000473:pathology; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020382:Interleukin-18 / Q000276:immunology / Q000378:metabolism*; D009061:Mouth Mucosa / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D012463:Saliva / Q000378:metabolism; D015854:Up-Regulation
D020382:Interleukin-18; D007371:Interferon-gamma