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Effects of activated macrophages on Nacardia asteroides
Abstract:
The mechanism(s) of host resistance against Nocardia asteroides has not been well defined. Since disease due to N. asteroides frequently occurs in patients with impaired cell-mediated immunity, we studied the interaction of N. asteroides with activated and control mouse peritoneal macrophages. Activated macrophages were from mice infected with Toxoplasma gondii or injected with Corynebacterium parvum. N. asteroides in the early stationary phase (>99% in the coccobacillary form) was used for challenge of macrophage monolayers. Growth of two strains of N. asteroides was markedly inhibited in activated macrophages, whereas N. asteroides grew well in control macrophages. Quantitation of macrophage-associated N. asteroides indicated that activated macrophages killed 40 to 50% of N. asteroides within 6 h (P < 0.002). In control macrophage preparations, it appeared as if Nocardia filaments extended from within macrophages to the outside, and many of these filaments appeared to have extended to and then grown through neighboring macrophages. In activated macrophage preparations, Nocardia remained in the coccobacillary form in most macrophages. Control macrophage monolayers were almost completely overgrown with and destroyed by Nocardia 20 h after challenge, whereas activated macrophage monolayers remained intact. Nocardia that grew in control macrophages were not acid-alcohol fast or only weakly so, whereas the few Nocardia that grew in activated macrophages were strongly acid-alcohol fast. Our results indicate that activated macrophages may be important in host defense against N. asteroides.
Insights
Activated macrophages effectively inhibit Nocardia asteroides growth and kill the bacteria, suggesting their crucial role in host defense against nocardiosis, especially in immunocompromised individuals.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Host resistance mechanisms against Nocardia asteroides remain poorly understood.
- Nocardia asteroides infections commonly affect individuals with compromised cell-mediated immunity.
Purpose of the Study:
- To investigate the interaction between Nocardia asteroides and activated versus control mouse peritoneal macrophages.
- To elucidate the role of activated macrophages in controlling Nocardia asteroides infection.
Main Methods:
- Mouse peritoneal macrophages were activated using Toxoplasma gondii infection or Corynebacterium parvum injection.
- Macrophage monolayers were challenged with Nocardia asteroides in its coccobacillary form.
- Bacterial growth, killing rates, and morphological changes within macrophages were quantified.
Main Results:
- Activated macrophages significantly inhibited Nocardia asteroides growth compared to control macrophages.
- Activated macrophages killed 40-50% of Nocardia asteroides within 6 hours.
- Nocardia asteroides remained in coccobacillary form in activated macrophages, while filaments formed and destroyed control monolayers.
Conclusions:
- Activated macrophages play a critical role in host defense against Nocardia asteroides.
- Enhanced bacterial killing and inhibition of filamentation by activated macrophages are key mechanisms of resistance.