Candidalysin is required for neutrophil recruitment and virulence during systemic Candida albicans infection.
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.