期刊
JOURNAL OF INFECTIOUS DISEASES
卷 220, 期 9, 页码 1477-1488出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiz322
关键词
Candida albicans; candidalysin; fungal; systemic; endothelial
资金
- Wellcome Trust [214229_Z_18_Z]
- Biotechnology and Biological Sciences Research Council [BB/N014677/1]
- National Institutes of Health (NIH) [R37-DE022550]
- King's Health Partners Challenge Fund [R170501]
- NIH Research at Guys and St. Thomas's NHS Foundation Trust and the King's College London Biomedical Research Centre [IS-BRC-1215-20006]
- National Institutes of Health [K99DE026856, R01DE022600, R01AI124566]
- Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, NIH
- Deutsche Forschungsgemeinschaft [EXC 22167-390884018, CRC/TR 124]
- BBSRC [BB/N014677/1] Funding Source: UKRI
- MRC [MC_PC_16048, MR/J008303/1] Funding Source: UKRI
Background. 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. Methods. In this study, using candidalysin-producing and candidalysin-deficient C albicans strains, we show that candidalysin activates mitogen-activated protein kinase (MAPK) signaling and chemokine secretion in endothelial cells in vitro. Results. Candidalysin induces immune activation and neutrophil recruitment in vivo, and it promotes mortality in zebrafish and murine models of systemic fungal infection. Conclusions. The data demonstrate a key role for candidalysin in neutrophil recruitment and fungal virulence during disseminated systemic C albicans infections.
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