title: Induction of caspase-11 by aspartyl proteinases of Candida albicans and implication in promoting inflammatory response.
abstract: We recently demonstrated that the secreted aspartyl proteinases (Saps), Sap2 and Sap6, of Candida albicans have the potential to induce the canonical activation of the NLRP3 inflammasome, leading to the secretion of interleukin-1β (IL-1β) 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 interferon (IFN) production. Caspase-11 cooperates to activate caspase-1, with a subsequent increase of IL-1β secretion. Endocytosis and internalization of Saps are required for the induction of type I IFN production, which is essential for induction of noncanonical inflammasome activation. Our study indicates a sophisticated interplay between caspase-1 and caspase-11 that connects the canonical and noncanonical pathways of inflammasome activation in response to C. albicans Saps.
authors.affiliation: Microbiology Section, Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Gabrielli
authors.affiliation: Microbiology Section, Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Pericolini
authors.affiliation: Microbiology Section, Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Luciano
authors.affiliation: Microbiology Section, Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Samuele
authors.initials: S
authors.lastname: Sabbatini
authors.affiliation: Microbiology Section, Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Roselletti
authors.affiliation: Microbiology Section, Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Perito
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany.
authors.forename: Lydia
authors.initials: L
authors.lastname: Kasper
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany Friedrich Schiller University, Jena, Germany Center for Sepsis Control and Care, Jena, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hube
authors.affiliation: Microbiology Section, Department of Experimental Medicine, University of Perugia, Perugia, Italy anna.vecchiarelli@unipg.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Vecchiarelli
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002176:Candida albicans / Q000201:enzymology*; D020170:Caspase 1 / Q000378:metabolism; D020169:Caspases / Q000032:analysis*; D053471:Caspases, Initiator; D002460:Cell Line; D004705:Endocytosis; D005260:Female; D005656:Fungal Proteins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000473:pathology*; D007370:Interferon Type I / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008810:Mice, Inbred C57BL
chemical_list: D005656:Fungal Proteins; D058847:Inflammasomes; D007370:Interferon Type I; C101136:Casp4 protein, mouse; D020169:Caspases; D053471:Caspases, Initiator; D020170:Caspase 1; D016282:Aspartic Acid Endopeptidases; C090753:SAP2 protein, Candida; C582621:SAP6 protein, Candida albicans