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The Mycobacterium tuberculosis phagosome interacts with early endosomes and is accessible to exogenously administered
1Department of Medicine, UCLA School of Medicine 90095, USA.
Abstract:
Previous studies have demonstrated that the Mycobacterium tuberculosis phagosome in human monocyte-derived macrophages acquires markers of early and late endosomes, but direct evidence of interaction of the M. tuberculosis phagosome with the endosomal compartment has been lacking. Using the cryosection immunogold technique, we have found that the M. tuberculosis phagosome acquires exogenously added transferrin in a time-dependent fashion. Near-maximal acquisition of transferrin occurs within 15 min, kinetics of acquisition consistent with interaction of the M. tuberculosis phagosome with early endosomes. Transferrin is chased out of the M. tuberculosis phagosome by incubation of the infected macrophages in culture medium lacking human transferrin. Phagosomes containing latex beads or heat-killed M. tuberculosis, on the other hand, do not acquire staining for transferrin. These and other findings demonstrate that M. tuberculosis arrests the maturation of its phagosome at a stage at which the phagosome interacts with early and late endosomes, but not with lysosomes. The transferrin endocytic pathway potentially provides a novel route for targeting antimicrobials to the M. tuberculosis phagosome.
Insights
Mycobacterium tuberculosis phagosomes interact with early and late endosomes, but not lysosomes. This interaction suggests a new way to deliver antimicrobials to tuberculosis infection sites.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Mycobacterium tuberculosis (M. tuberculosis) resides within phagosomes in macrophages.
- Previous studies suggest M. tuberculosis phagosomes acquire early and late endosomal markers, but direct interaction evidence was lacking.
Purpose of the Study:
- To provide direct evidence of M. tuberculosis phagosome interaction with the endosomal pathway.
- To investigate the maturation stage of the M. tuberculosis phagosome within macrophages.
Main Methods:
- Utilized cryosection immunogold technique to track transferrin uptake.
- Incubated M. tuberculosis-infected macrophages with transferrin and monitored its acquisition and clearance.
- Compared transferrin uptake in M. tuberculosis phagosomes versus phagosomes with latex beads or heat-killed M. tuberculosis.
Main Results:
- M. tuberculosis phagosomes acquired exogenously added transferrin in a time-dependent manner, peaking within 15 minutes.
- Transferrin was chased out of M. tuberculosis phagosomes, indicating dynamic interaction with the early endosome pathway.
- Phagosomes containing latex beads or heat-killed M. tuberculosis did not acquire transferrin, highlighting M. tuberculosis-specific interaction.
Conclusions:
- M. tuberculosis actively arrests phagosome maturation, maintaining interaction with early and late endosomes but excluding lysosomes.
- The transferrin endocytic pathway presents a potential novel route for antimicrobial drug delivery to the M. tuberculosis phagosome.
- Understanding phagosome-endosome dynamics is crucial for developing effective tuberculosis therapies.