In vitro analyses of tissue structure and interleukin-1beta expression and production by human oral mucosa in response to Candida albicans infections.

摘要

Clinical and experimental observations suggest that oral epithelial cells play a key role in host defenses against candidal infections through cytokines and chemokines. We thus attempted to determine whether oral epithelial cells convey IL-1beta as a pro-inflammatory cytokine in response to Candida albicans infections. We created engineered human oral mucosa (EHOM), put them in contact with live and heat-inactivated C. albicans (10(5) yeast/cm2), and measured the expression of IL-1beta mRNA and protein. Tissue structure and C. albicans morphology were also evaluated. Only live C. albicans modulated IL-1beta expression and secretion. IL-1beta mRNA expression significantly increased during the early stages of infection and decreased during the later stages. The modulatory effect of C. albicans on IL-1beta expression was confirmed by the fact that increased amounts of inactive IL-1beta (33 kDa) were detected early during the infection which then dropped dramatically. There was a significant and time-dependent increase in the amount of the active form of IL-1beta (17 kDa) secreted into the supernatant by epithelial cells infected with live C. albicans. Histological features revealed damage to infected tissues (separation of epithelial cells, edema, vacuolization, reduction in thickness) compared to uninfected ones. Morphological analyses showed that C. albicans changed from a blastospore to a hyphal form at later infection periods. This transformation was very pronounced at 8 and 24 h post-infection. These results provide additional evidence for the contribution of oral epithelial cells to local defenses against exogenous stimulations such as C. albicans infections.