Direct interaction studies between Aspergillus fumigatus and human immune cells; what have we learned about
Charles O Morton1, Maria Bouzani, Juergen Loeffler
1School of Science and Health, University of Western Sydney Campbelltown, NSW, Australia.
Abstract:
Invasive aspergillosis is a significant threat to health and is a major cause of mortality in immunocompromised individuals. Understanding the interaction between the fungus and the immune system is important in determining how the immunocompetent host remains disease free. Several studies examining the direct interaction between Aspergillus fumigatus and purified innate immune cells have been conducted to measure the responses of both the host cells and the pathogen. It has been revealed that innate immune cells have different modes of action ranging from effective fungal killing by neutrophils to the less aggressive response of dendritic cells. Natural killer cells do not phagocytose the fungus unlike the other innate immune cells mentioned but appear to mediate their antifungal effect through the release of gamma interferon. Transcriptional analysis of A. fumigatus interacting with these cells has indicated that it can adapt to the harsh microenvironment of the phagosome and produces toxins, ribotoxin and gliotoxin, that can induce cell death in the majority of innate immune cells. These data point toward potential novel antifungal treatments including the use of innate immune cells as antifungal vaccines.
Insights
Investigating Aspergillus fumigatus interactions with innate immune cells reveals fungal toxins induce immune cell death. This suggests novel antifungal therapies using immune cells as vaccines.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Invasive aspergillosis poses a significant health threat, particularly to immunocompromised individuals.
- Understanding host-pathogen interactions is crucial for preventing invasive fungal infections.
Purpose of the Study:
- To investigate the interaction between Aspergillus fumigatus and various innate immune cells.
- To elucidate the mechanisms by which the innate immune system combats Aspergillus fumigatus.
- To identify fungal adaptations and host responses during infection.
Main Methods:
- Co-culture of Aspergillus fumigatus with purified human innate immune cells (neutrophils, dendritic cells, natural killer cells).
- Measurement of immune cell responses and fungal viability.
- Transcriptional analysis of Aspergillus fumigatus during host cell interaction.
- Detection of fungal-derived toxins (ribotoxin, gliotoxin).
Main Results:
- Innate immune cells exhibit varied responses: neutrophils effectively kill fungi, while dendritic cells show less aggressive action.
- Natural killer cells utilize gamma interferon for antifungal effects, distinct from phagocytosis.
- Aspergillus fumigatus adapts to the phagosome, producing ribotoxin and gliotoxin.
- These toxins induce cell death in most innate immune cells.
Conclusions:
- Aspergillus fumigatus employs potent toxins to evade and damage the innate immune system.
- Innate immune cells display diverse antifungal mechanisms.
- These findings suggest potential novel antifungal strategies, including the development of antifungal vaccines based on innate immune cells.
