PUBLICATION
Candidalysin Is Required for Neutrophil Recruitment and Virulence During Systemic Candida albicans Infection
- Authors
- Swidergall, M., Khalaji, M., Solis, N.V., Moyes, D.L., Drummond, R.A., Hube, B., Lionakis, M.S., Murdoch, C., Filler, S.G., Naglik, J.R.
- ID
- ZDB-PUB-190812-3
- Date
- 2019
- Source
- The Journal of infectious diseases 220(9): 1477-1488 (Journal)
- Registered Authors
- Keywords
- Candida albicans, candidalysin, endothelial, fungal, systemic
- MeSH Terms
-
- Animals
- Candida albicans/growth & development
- Candida albicans/immunology*
- Candida albicans/metabolism*
- Candidiasis, Invasive/microbiology*
- Candidiasis, Invasive/pathology*
- Cytokines/metabolism
- Disease Models, Animal
- Endothelial Cells/drug effects
- Endothelial Cells/immunology
- Endothelial Cells/metabolism
- Female
- Fungal Proteins/metabolism*
- Male
- Mice, Inbred BALB C
- Neutrophil Infiltration*
- Signal Transduction
- Survival Analysis
- Virulence
- Virulence Factors/metabolism*
- Zebrafish
- PubMed
- 31401652 Full text @ J. Infect. Dis.
Citation
Swidergall, M., Khalaji, M., Solis, N.V., Moyes, D.L., Drummond, R.A., Hube, B., Lionakis, M.S., Murdoch, C., Filler, S.G., Naglik, J.R. (2019) Candidalysin Is Required for Neutrophil Recruitment and Virulence During Systemic Candida albicans Infection. The Journal of infectious diseases. 220(9):1477-1488.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping