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T-cell-mediated immunity in persistent Mycobacterium intracellulare infections in mice
1Trudeau Institute, Inc., Saranac Lake, New York 12983.
Abstract:
Growth of mouse-virulent Mycobacterium intracellulare D673 and TMC 1405 in the lung was affected by T-cell depletion in susceptible C57BL/6 mice. Significant differences also occurred between the growth patterns seen in congenitally athymic (nu/nu) mice and their nu/+ littermates. Treatment of the mice with an immunosuppressive regimen of cyclosporin A (75 mg/kg of body weight per day subcutaneously) provided further evidence of the importance of T cells in controlling growth of M. intracellulare in the normal host. Adoptive transfer experiments indicated the presence of a T-cell-mediated specific protective immunity against a subsequent M. intracellulare challenge when transfer was carried out 3 weeks after immunization of the donor host. At this time, cross-protective immunity was also observed against a virulent M. tuberculosis challenge. There was no difference in the rate of growth by M. intracellulare as challenge in Mycobacterium bovis BCG-activated or normal peritoneal macrophages from C57BL/6 mice tested in vitro during a 7-day period. However, M. tuberculosis growth rates were decreased substantially in the BCG-activated macrophages. These studies suggest that mice infected with M. intracellulare do not eliminate the infection, because this organism can resist the bactericidal activity of the T-cell-activated macrophage better than M. tuberculosis can.
Insights
T-cell immunity is crucial for controlling Mycobacterium intracellulare lung infections in mice. This bacterium resists T-cell-activated macrophages more effectively than Mycobacterium tuberculosis, hindering infection clearance.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- T-cell depletion impacts Mycobacterium intracellulare growth in susceptible mice.
- Congenitally athymic mice exhibit different growth patterns compared to their heterozygous littermates.
Purpose of the Study:
- To investigate the role of T cells in controlling Mycobacterium intracellulare infection.
- To explore the mechanisms of resistance and cross-protection against mycobacterial infections.
Main Methods:
- T-cell depletion using specific treatments.
- Comparison of bacterial growth in athymic and normal mice.
- Immunosuppression with cyclosporin A.
- Adoptive transfer of immune T cells.
- In vitro macrophage activation assays.
Main Results:
- T-cell depletion significantly affected M. intracellulare growth.
- Cyclosporin A treatment highlighted the importance of T cells.
- Adoptive transfer induced specific and cross-protective immunity.
- M. intracellulare resisted bactericidal activity of activated macrophages, unlike M. tuberculosis.
Conclusions:
- T cells play a critical role in managing M. intracellulare infections.
- M. intracellulare's resistance to T-cell-activated macrophages contributes to persistent infection.
- Understanding these mechanisms may inform therapeutic strategies for mycobacterial diseases.