Programmpunkt

14:00

Titel: The Candida albicans peptide toxin Candidalysin causes cytolysis and activates the NLRP3 inflammasome in mononuclear phagocytes
ID: 8/EKV
Art: Abstractautor
Session: Workshop 02
Eukaryotic Pathogens incl. DMykG Lecture (FG EK)

Referent: Lydia Kasper (Jena)


Abstract - Text

Clearance of invading microbes requires phagocytes of the innate immune system. However, successful pathogens have evolved sophisticated strategies to evade killing by these immune cells. The opportunistic human fungal pathogen Candida albicans is efficiently phagocytosed by macrophages but causes inflammasome activation, damages the host cells, and escapes after hypha formation. Previous studies suggest that macrophage lysis by C. albicans results from early inflammasome-dependent cell death (pyroptosis) followed by late damage due to glucose depletion and membrane piercing by growing hyphae.

We are interested in the role of Candidalysin, a cytolytic peptide toxin encoded by the hypha-associated gene ECE1. We have previously shown that Candidalysin directly damages epithelial membranes and triggers an epithelial danger response. Here we describe that Candidalysin is a central trigger for NLRP3 inflammasome-dependent caspase-1 activation via potassium efflux in human macrophages, murine macrophages and murine dendritic cells. In addition, Candidalysin induces inflammasome-independent cytolysis in these immune cells upon infection with C. albicans. This suggests that Candidalysin-induced cell lysis is a third mechanism of C. albicans-mediated phagocyte damage in addition to damage caused by pyroptosis and by the growth of glucose-consuming hyphae.

Candidalysin is one of eight short peptides encoded by ECE1 and released from the Ece1 polyprotein after processing. While a major contribution of Candidalysin to fungal pathogenicity and anti-fungal immune response is clear, the function of the non-Candidalysin Ece1 peptides remains obscure. Future studies will, therefore, characterize the potential role of non-Candidalysin Ece1 peptides in fungal biology and host interaction.