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Normal and deficient neutrophils can cooperate to damage Aspergillus fumigatus hyphae
J H Rex1, J E Bennett, J I Gallin
1Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Abstract:
Using a metabolic test of hyphal viability, the interaction between neutrophils and Aspergillus hyphae was investigated over a broad range of hyphae-to-neutrophil ratios. Normal neutrophils were found to damage hyphae whereas neutrophils from patients with both chronic granulomatous disease (CGD) and myeloperoxidase (MPO) deficiency did not. Further, both azide and catalase + superoxide dismutase inhibited the ability of normal neutrophils to damage hyphae, suggesting that this damage is mediated by products of the respiratory burst and by the MPO-halide system. Also, mixtures of small numbers of normal neutrophils with larger numbers of CGD neutrophils (range, 1:5 to 1:15) damaged hyphae more efficiently than either population of cells alone. Further, mixtures of CGD and MPO-deficient neutrophils, neither of which alone could efficiently damage hyphae, were able to damage the hyphae almost as well as a comparable number of normal neutrophils. These data demonstrate that intact neutrophils can cooperate to synergistically damage Aspergillus hyphae, possibly by extracellular mixing of hydrogen peroxide and MPO.
Insights
Neutrophils damage Aspergillus fungi through respiratory burst products and the myeloperoxidase (MPO)-halide system. Neutrophil cooperation, involving hydrogen peroxide and MPO, enhances this fungal damage.
Area of Science:
- Immunology
- Mycology
- Cell Biology
Background:
- Neutrophils are critical immune cells for combating fungal infections.
- Aspergillus hyphae pose a significant threat, particularly to immunocompromised individuals.
- Understanding neutrophil-fungal interactions is key to developing effective antifungal strategies.
Purpose of the Study:
- To investigate the mechanisms by which neutrophils damage Aspergillus hyphae.
- To determine the role of the respiratory burst and myeloperoxidase (MPO) in neutrophil-mediated hyphal damage.
- To explore the synergistic effects of different neutrophil populations on fungal viability.
Main Methods:
- Metabolic testing of hyphal viability was employed.
- Neutrophil-fungal interactions were studied across various hyphae-to-neutrophil ratios.
- Experiments utilized normal neutrophils, neutrophils from chronic granulomatous disease (CGD) patients, and MPO-deficient neutrophils.
Main Results:
- Normal neutrophils effectively damaged Aspergillus hyphae.
- Neutrophils from CGD and MPO-deficient patients showed impaired hyphal damage.
- Inhibition of respiratory burst products (azide) or MPO-halide system components (catalase + superoxide dismutase) reduced normal neutrophil efficacy.
- Mixtures of normal and CGD neutrophils, or CGD and MPO-deficient neutrophils, demonstrated synergistic damage to hyphae.
Conclusions:
- Neutrophil-mediated damage to Aspergillus hyphae is primarily mediated by reactive oxygen species from the respiratory burst and the MPO-halide system.
- Cooperation between neutrophils, potentially through extracellular mixing of hydrogen peroxide and MPO, significantly enhances the synergistic damage to fungi.
- These findings highlight the importance of neutrophil functional integrity and cooperation in antifungal defense.