Secreted aspartic proteases of Candida albicans activate the NLRP3 inflammasome.
作者： Donatella Pietrella , Neelam Pandey , Elena Gabrielli , Eva Pericolini , Stefano Perito
关键词:
摘要: In a recent report, we demonstrated that distinct members of the secreted aspartic protease (Sap) family Candida albicans are able to induce secretion proinflammatory cytokines by human monocytes, independently their proteolytic activity and specific pH optima. particular, C. Sap2 Sap6 potently induced IL-1β, TNF-α, IL-6 production. Here, demonstrate proteins trigger IL-1β IL-18 production through inflammasome activation. This occurs via NLRP3 caspase-1 activation, which cleaves pro-IL-1β into bioactive cytokine was Saps in monocyte-derived macrophages dendritic cells. Downregulation RNA interference strongly reduced IL-1β. Inflammasome activation required Sap internalization clathrin-dependent mechanism, intracellular induction K+ efflux, ROS monocytes differed from LPS-ATP several aspects. Our data reveal novel immunoregulatory mechanisms suggest contribute pathogenesis candidiasis fostering rather than evading host immunity.
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