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Differential recruitment of CD63 and Rab7-interacting-lysosomal-protein to phagosomes containing Mycobacterium
Shintaro Seto1, Sohkichi Matsumoto, Kunio Tsujimura
1Department of Infectious Diseases, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
Abstract:
M.tb is an intracellular pathogen which survives within the phagosomes of host macrophages by inhibiting their fusion with lysosomes. Here, it has been demonstrated that a lysosomal glycoprotein, CD63, is recruited to the majority of M.tb phagosomes, while RILP shows limited localization. This is consistent with the author's findings that CD63, but not RILP, is recruited to the phagosomes in macrophages expressing the dominant negative form of Rab7. These results suggest that M.tb phagosomes selectively fuse with endosomes and lysosomes to escape killing activity while acquiring nutrients.
Insights
Mycobacterium tuberculosis (M.tb) evades immune cells by preventing phagosome-lysosome fusion. CD63 protein is recruited to M.tb phagosomes, aiding survival by enabling nutrient acquisition and preventing bacterial killing.
Area of Science:
- Cell Biology
- Immunology
- Microbiology
Background:
- Mycobacterium tuberculosis (M.tb) is an intracellular pathogen that resides within macrophage phagosomes.
- M.tb inhibits phagosome-lysosome fusion, a key mechanism for host defense and bacterial clearance.
Purpose of the Study:
- To investigate the role of specific proteins, CD63 and RILP, in M.tb phagosome maturation.
- To understand how M.tb manipulates host cell pathways for survival.
Main Methods:
- Immunofluorescence microscopy to detect protein localization on M.tb phagosomes.
- Use of macrophages expressing dominant-negative Rab7 to assess protein recruitment pathways.
Main Results:
- CD63, a lysosomal glycoprotein, is significantly recruited to the majority of M.tb phagosomes.
- RILP shows limited localization to M.tb phagosomes.
- CD63 recruitment is dependent on Rab7, while RILP recruitment is not.
Conclusions:
- M.tb phagosomes selectively fuse with endosomes and lysosomes, mediated by proteins like CD63.
- This selective fusion allows M.tb to evade lysosomal killing mechanisms and acquire essential nutrients for intracellular survival.
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