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Proteolytic Activation of the Interleukin1β Precursor by Candida albicans

Proteolytic Activation of the Interleukin1β Precursor by Candida albicans

Beauséjour, Annie, Grenier, Daniel, Goulet, JeanPaul

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‐1β (IL‐1β) 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‐1β (pro‐IL‐1β) 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‐1β to yield fragments of molecular masses compatible with mature biologically active IL‐1β (17 to 19 kDa). Assays conducted in the presence of selected proteinase inhibitors suggest that the cleavage of pro‐IL‐1β involves the participation of one or more aspartyl proteinases. Cleavage products showed a dose‐dependent IL‐1β‐like activity in a thymocyte proliferation bioassay, which was inhibited by anti‐IL‐1β 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.


Keywords: chronic inflammation proteinase pathogenesis cytokine advanced

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