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Experimental visceral aspergillosis
Abstract:
Studies conducted to gain insight into the pathogenesis of experimental aspergillosis indicated that mice pretreated with cortisone acetate and then injected intraperitoneally with nongerminating spores of Aspergillus flavus developed a high incidence of lethal visceral hyphal aspergillosis. A similar, high incidence of fatal infections was observed in cortisone-treated animals in which the number of peritoneal macrophages had been increased by prior injection of thioglycollate. To determine whether germination of spores within the host was important to the subsequent development of disseminated hyphal aspergillosis, germinating spores of A flavus were injected intraperitoneally into normal animals. While a similar dose of nongerminating spores, administered intraperitoneally into normal mice, induced a low incidence of lethal injection, germinating spores induced a high incidence of fatal disease associated with widely disseminated visceral hyphal aspergillosis. Our studies indicate that phagocytic cells in the peritoneal cavity of normal mice are able to ingest nonperminating spores of A flavus and kill them, preventing germination. However, the phagocytic cells are unable to cope with early germinating spores, which then continue to proliferate, leading to extensive hyphal invasion of visceral organs and death.
Insights
Germinating Aspergillus flavus spores cause lethal infections in mice, overwhelming immune defenses. Non-germinating spores are cleared by phagocytic cells, preventing invasive aspergillosis.
Area of Science:
- Mycology
- Immunology
- Pathogenesis
Background:
- Experimental aspergillosis pathogenesis is not fully understood.
- Immune suppression can increase susceptibility to fungal infections.
Purpose of the Study:
- To investigate the role of Aspergillus flavus spore germination in the development of invasive aspergillosis.
- To determine the efficacy of phagocytic cells in clearing fungal spores.
Main Methods:
- Mice were pretreated with cortisone acetate or thioglycollate to modulate immune responses.
- Intraperitoneal injection of germinating and non-germinating Aspergillus flavus spores.
- Observation of infection incidence, dissemination, and mortality.
Main Results:
- Cortisone acetate-treated mice developed lethal visceral hyphal aspergillosis after infection with non-germinating spores.
- Germinating Aspergillus flavus spores induced a high incidence of fatal disease in normal mice.
- Phagocytic cells cleared non-germinating spores but failed to control early germinating spores.
Conclusions:
- Spore germination is critical for the development of disseminated hyphal aspergillosis.
- Early germinating spores evade phagocytic clearance, leading to invasive disease.
- Immune status significantly impacts the outcome of Aspergillus flavus infection.