Proteolytic activation of the interleukin-1β precursor by Candida albicans

Chronic inflammation rather than invasion is characteristic of some forms of superficial candidiasis such as denture stomatitis. We hypothesized that Candida albicans may play a critical role in the pathogenesis of inflammatory lesions observed in chronic candidiasis by activating the proinflammatory cytokine interleukin-1 beta (IL-1 beta) from epithelial stores of the precursor, The aim of this study was therefore to demonstrate the proteolytic cleavage and activation of the inactive precursor of IL-1 beta (pro-IL-1 beta) by C. albicans, After incubation of either blastospores or hyphae with the inactive precursor, proteolytic cleavage was monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis Western immunoblotting analysis, and the biological activity of the cleavage products was tested in a bioassay, We report here that late-stationary-growth-phase blastospores as well as hyphae of C. albicans, but not exponentially growing cells, can efficiently cleave pro-IL-1 beta to yield fragments of molecular masses compatible with mature biologically active IL-1 beta (17 to 19 kDa), Assays conducted in the presence of selected proteinase inhibitors suggest that the cleavage of pro-IL-1 beta involves the participation of one or more aspartyl proteinases. Cleavage products showed a dose-dependent IL-1 beta-like activity in a thymocyte proliferation bioassay, which was inhibited by anti-IL-1 beta neutralizing antibodies, The present data thus suggest a role for C, albicans proteinases in the activation and maintenance of the inflammatory response at epithelial surfaces.