Aspartyl proteinases of Candida albicans induce caspase-11: implication in promoting inflammatory response

We recently demonstrated that the secreted aspartyl proteinases (Saps), Sap2 and Sap6, of Candida albicans have the potential to induce the canonical activation of NLRP3-inflammasome leading to the secretion of IL-1beta and IL-18 via caspase-1 activation. We also observed that the activation of caspase-1 is partially independent from the NLRP3 activation pathway. In this study, we examined whether Sap2 and Sap6 are also able to activate the noncanonical inflammasome pathway in murine macrophages. Our data show that both, Sap2 and Sap6, can activate caspase-11 through type I IFN production. Caspase-11 concurs to activate caspase-1 with subsequent increase of IL-1beta secretion. Endocytosis and internalization of Saps are required for the induction of type I IFN production, that is essential for induction of noncanonical inflammasome activation. Our study indicates a sophisticated interplay between caspase-1 and caspase-11 that connects canonical and noncanonical pathways of inflammasome activation in response to Candida albicans Saps.