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Fungicidal activation of murine macrophages by recombinant gamma interferon
1Medical Microbiology and Immunology, University of California School of Medicine, Davis 95616.
Abstract:
Alveolar macrophages from BALB/c mice readily phagocytized endospores (2 to 5 micron) and arthroconidia of Coccidioides immitis in vitro. Within 24 to 30 h at 37 degrees C, the phagocytized endospores started developing into spherules, and the arthroconidia formed germ tubes and hyphae. However, these processes did not occur if the macrophages were incubated with murine recombinant gamma interferon (rIFN-gamma) during infection with C. immitis. Treatment with rIFN-gamma activated the fungicidal capabilities of the alveolar macrophages, as evidenced by the 50% reduction in the CFU which could be recovered from macrophages infected in the presence of gamma interferon compared with alveolar macrophages infected without gamma interferon (P less than 0.05). Similar results were seen with peritoneal macrophages incubated with rIFN-gamma and infected with C. immitis. As little as 10 U of rIFN-gamma per ml reduced by half the number of C. immitis CFU which could be recovered from the phagocytes 8 h after infection with arthroconidia, although interferon alone did not affect the viability of the fungi.
Insights
Murine recombinant gamma interferon (rIFN-gamma) activates alveolar macrophages to kill Coccidioides immitis. This immune response prevents fungal development within macrophages, crucial for controlling Coccidioides infection.
Area of Science:
- Immunology
- Mycology
- Microbiology
Background:
- Alveolar macrophages are key immune cells in the lungs.
- Coccidioides immitis is a fungal pathogen causing coccidioidomycosis.
- Fungal development within macrophages can lead to disease progression.
Purpose of the Study:
- To investigate the effect of murine recombinant gamma interferon (rIFN-gamma) on Coccidioides immitis infection in macrophages.
- To determine if rIFN-gamma can enhance the fungicidal activity of macrophages against C. immitis.
Main Methods:
- In vitro infection of BALB/c mouse alveolar and peritoneal macrophages with Coccidioides immitis endospores and arthroconidia.
- Incubation of infected macrophages with and without murine recombinant gamma interferon (rIFN-gamma).
- Assessment of fungal development (spherule formation, germ tube growth) and quantification of viable fungal Colony Forming Units (CFU).
Main Results:
- Phagocytized C. immitis endospores developed into spherules and arthroconidia formed hyphae within macrophages in vitro.
- rIFN-gamma treatment inhibited fungal development within macrophages.
- rIFN-gamma significantly enhanced the fungicidal activity of both alveolar and peritoneal macrophages, reducing C. immitis CFU by 50% (P < 0.05).
- As little as 10 U/ml of rIFN-gamma halved the recoverable C. immitis CFU after 8 hours of infection with arthroconidia.
Conclusions:
- Murine recombinant gamma interferon (rIFN-gamma) activates macrophages to exhibit potent fungicidal activity against Coccidioides immitis.
- rIFN-gamma inhibits the intracellular development of C. immitis, preventing spherule and hyphal formation within macrophages.
- These findings suggest that rIFN-gamma plays a critical role in controlling Coccidioides immitis infections by enhancing macrophage-mediated immunity.