Mechanisms of Resistance of Aspergillus fumigatus Conidia to Killing by Neutrophils in Vitro

• Published in: The Journal of infectious diseases 1985-07, Vol.152 (1), p.33-42
• Main Authors: Levitz, Stuart M., Diamond, Richard D.
• Format: Article
• Language: English
• Subjects: Aspergillosis; Aspergillus fumigatus - drug effects; Aspergillus fumigatus - immunology; Aspergillus fumigatus - physiology; Biological and medical sciences; Blood Bactericidal Activity; Candida albicans - physiology; Cell walls; Conidia; Fundamental and applied biological sciences. Psychology; Fungal spores; Fungi; Humans; Hydrogen Peroxide - metabolism; Hydrogen Peroxide - pharmacology; Hyphae; Hypochlorous Acid - metabolism; Hypochlorous Acid - pharmacology; Membrane Fusion; Microbiology; Mycology; Neutrophils; Neutrophils - immunology; Neutrophils - metabolism; Neutrophils - microbiology; Original Articles; Oxygen Consumption; Pathogenicity, host-agent relations, miscellaneous strains, epidemiology; Peroxidase - metabolism; Phagocytosis; Reagents; Rose Bengal - pharmacology; Spores, Fungal - drug effects; Spores, Fungal - immunology; Superoxides; Superoxides - metabolism
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/152.1.33

Despite the critical role for neutrophils in host defenses against invasiveaspergillosis, previous studies have established that neutrophils are unable to kill resting conidia of Aspergillusfumigatus. The mechanisms of resistance of the conidia were therefore investigated. Electron microscopy studies showed the fusion of phagosomes containing A. fumigatus conidia with lysosomes of the neutrophil. Resting conidia of A. fumigatus were then compared with those that had been preincubated in broth until swollen, but not germinated, as well as with blastospores of Candida albicans (two fungal forms that are killed by neutrophils) and zymosan particles. Despite comparable susceptibility to phagocytosis, resting conidia of A. fumigatus stimulated production of significantly less superoxide anion, hydrogen peroxide, and hypochlorous acid and induced less myeloperoxidase-dependent iodination by neutrophils than did the preincubated conidia of A. fumigatus, blastospores of C. albicans, or zymosan particles. In addition, resting conidia of A. fumigatus were relatively resistant to cell-free killing by oxidants presumed to be generated by neutrophils. Thus, resistance of resting conidia of A. fumigatus to neutrophil fungicidal mechanisms appears to be secondary to both failure of the conidia to stimulate an optimal respiratory burst as well as resistance of the conidia to neutrophil oxidants. However, the reversal of this resistance by preincubation of the conidia suggests that neutrophils still may form an important host defense against the conidia of A. fumigatus.