Abstract

Candidalysin is a cytolytic peptide toxin secreted by Candida albicans hyphae and has significantly advanced our understanding of fungal pathogenesis. Candidalysin is critical for mucosal C. albicans infections and is known to activate epithelial cells to induce downstream innate immune responses that are associated with protection or immunopathology during oral or vaginal infections. Furthermore, candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes. However, the role of candidalysin in driving systemic infections is unknown. Here, using candidalysin-producing and candidalysin-deficient C. albicans strains, we show that candidalysin activates mitogen-activated protein kinase (MAPK) signalling and chemokine secretion in endothelial cells in vitro. Furthermore, candidalysin induces immune activation and neutrophil recruitment in vivo, and promotes mortality in zebrafish and murine models of systemic fungal infection. The data demonstrate a key role for candidalysin in neutrophil recruitment and fungal virulence during disseminated systemic C. albicans infections.
Original languageEnglish
Pages (from-to)1477–1488
JournalJournal of Infectious Diseases
Volume220
Issue number9
Early online date11 Aug 2019
DOIs
Publication statusE-pub ahead of print - 11 Aug 2019

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