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Live Imaging of Antifungal Activity by Human Primary Neutrophils and Monocytes in Response to A. fumigatus
Published on: April 19, 2017
Hydrogen peroxide-induced secondary necrosis in conidia of Aspergillus fumigatus
M Oliveira1,2,3, C Pereira4, C Bessa4
1a Instituto de Investigação e Inovação em Saúde, Universidade Do Porto, Portugal.
Abstract:
Aspergillus fumigatus conidia have been linked to severe aspergillosis in immunocompromised patients. Recently, the cytotoxic effect of secondary metabolites from A. fumigatus conidia was reported. In the present work, a methodology used to detect cell death markers in fungal hyphae was adapted to study conidia cell death. Additionally, the mechanism of H2O2-induced cell death was studied in A. fumigatus conidia for the first time. Data presented in this work reveal that the H2O2-induced conidial cell death was associated with a marked increase of TUNEL- and PI-positive cells. It is therefore suggested that conidia cell death occurs in a dose-dependent manner through a secondary necrosis mechanism. The knowledge of conidia cell death machinery may provide insights into the molecular mechanism of conidia-mediated toxicity to the respiratory tract and may pave the way for improved therapeutic approaches against A. fumigatus conidia-mediated diseases.
Insights
Hydrogen peroxide (H2O2) induces cell death in Aspergillus fumigatus conidia via secondary necrosis. This finding offers new therapeutic targets for fungal diseases in immunocompromised patients.
Area of Science:
- Medical Mycology
- Cell Biology
- Toxicology
Background:
- Aspergillus fumigatus conidia are linked to severe aspergillosis in immunocompromised individuals.
- Secondary metabolites from A. fumigatus conidia exhibit cytotoxic effects.
- Understanding fungal cell death mechanisms is crucial for disease management.
Purpose of the Study:
- To adapt a cell death detection methodology for A. fumigatus conidia.
- To investigate the mechanism of hydrogen peroxide (H2O2)-induced conidial cell death.
- To elucidate the role of secondary necrosis in H2O2-mediated conidial death.
Main Methods:
- Adaptation of a cell death marker detection assay for fungal conidia.
- Treatment of A. fumigatus conidia with varying concentrations of H2O2.
- Assessment of cell death using TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) and Propidium Iodide (PI) staining.
Main Results:
- H2O2-induced cell death in A. fumigatus conidia was observed.
- A dose-dependent increase in TUNEL- and PI-positive conidia was detected.
- Conidial cell death occurred through a secondary necrosis pathway.
Conclusions:
- H2O2 induces conidial cell death in A. fumigatus via secondary necrosis.
- This mechanism is dose-dependent.
- Understanding conidial cell death provides insights into A. fumigatus pathogenesis and potential therapeutic strategies.
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