Interleukin-18 and gamma interferon production by oral epithelial cells in response to exposure to Candida albicans or lipopolysaccharide stimulation.
Oral candidiasis is a collective name for a group of disorders caused by the dimorphic fungus Candida albicans. Host defenses against C. albicans essentially fall into two categories: specific immune mechanisms and local oral mucosal epithelial cell defenses. Since oral epithelial cells secrete a variety of cytokines and chemokines in response to oral microorganisms and since C. albicans is closely associated with oral epithelial cells as a commensal organism, we wanted to determine whether interleukin-18 (IL-18) and gamma interferon (IFN-gamma) were produced by oral epithelial cells in response to C. albicans infection and lipopolysaccharide (LPS) stimulation. Our results showed that IL-18 mRNA and protein were constitutively expressed by oral epithelial cells and were down-regulated by Candida infections but increased following LPS stimulation. Both C. albicans and LPS significantly decreased pro-IL-18 (24 kDa) levels and increased active IL-18 (18 kDa) levels. This effect was IL-1beta-converting-enzyme dependent. The increase in active IL-18 protein levels promoted the production of IFN-gamma by infected cells. No effect was obtained with LPS. Although produced only at an early stage, secreted IFN-gamma seemed to be a preferential response by oral epithelial cells to C. albicans growth. These results provide additional evidence for the contribution of oral epithelial cells to local (direct contact) and systemic (IL-18 and IFN-gamma production) defense against exogenous stimulation such as C. albicans infection or LPS stimulation.
Rouabhia
Mahmoud
M
Faculté de médecine dentaire. GREB, Université Laval, Québec G1K 7P4, Canada. Mahmoud.rouabhia@fmd.ulaval.ca
Ross
Geneviève
G
Pagé
Nathalie
N
Chakir
Jamila
J
D002176:Candida albicans / Q000254:growth & development / Q000472:pathogenicity*; D002448:Cell Adhesion; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D009061:Mouth Mucosa / Q000166:cytology / Q000276:immunology*
D020382:Interleukin-18; D008070:Lipopolysaccharides; D007371:Interferon-gamma