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Macrophage interaction with mycobacteria including M. leprae
Acta Leprologica
|October 1, 1984
Summary
Pathogenic mycobacteria resist macrophage killing due to their cell walls. An electron transparent zone (ETZ) forms around Mycobacterium leprae and Mycobacterium avium within macrophages, inhibiting lysosomal enzymes and aiding bacterial survival.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Pathogenic mycobacteria exhibit resistance to macrophage bactericidal activity, primarily attributed to their cell wall composition.
- Mycobacterium tuberculosis may use sulfatides and polyglutamic acid to inhibit phagosome-lysosome fusion.
- Mycobacterium leprae and Mycobacterium lepraemurium are protected by a thick electron transparent zone (ETZ) composed of mycosides, which inhibits lysosomal enzyme diffusion.
Purpose of the Study:
- To investigate the timing and mechanism of electron transparent zone (ETZ) formation in mycobacteria within macrophages.
- To compare ETZ formation in Mycobacterium leprae and Mycobacterium avium after phagocytosis.
Main Methods:
- Mouse bone-marrow derived macrophages were infected with Mycobacterium leprae and Mycobacterium avium.
- Samples were analyzed using electron microscopy at various time points post-phagocytosis and during incubation.
- ETZ formation was also examined in macrophages infected with heat-killed mycobacteria.
Main Results:
- In Mycobacterium avium, ETZ formation occurred within 1-2 hours, appearing as a swelling of the bacterial cell wall's thin electron transparent layer as the outer polysaccharide layer disappeared.
- In Mycobacterium leprae, ETZ formed within 1 hour, but observations of a thin dense layer and a thick dense layer between the ETZ and phagosome membrane require further understanding.
- ETZ formation was rapid even with heat-killed bacteria, indicating it does not require active bacterial participation.
- The ETZ significantly reduced lysosomal enzyme diffusion to the bacteria in both species.
- Mycobacterium leprae demonstrated remarkable resistance, with no change in bacterial numbers or degradation over 3.5 months despite phagolysosomal acid phosphatase activity.
Conclusions:
- The electron transparent zone (ETZ) is a crucial defense mechanism for Mycobacterium leprae and Mycobacterium avium against macrophage bactericidal activity.
- ETZ formation is a rapid process initiated after phagocytosis and does not depend on the bacterium's active participation.
- The ETZ effectively impedes lysosomal enzyme access, contributing to the long-term survival of Mycobacterium leprae within macrophages.