[HTML][HTML] M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells

N van der Wel, D Hava, D Houben, D Fluitsma… - Cell, 2007 - cell.com
N van der Wel, D Hava, D Houben, D Fluitsma, M van Zon, J Pierson, M Brenner, PJ Peters
Cell, 2007cell.com
M. tuberculosis and M. leprae are considered to be prototypical intracellular pathogens that
have evolved strategies to enable growth in the intracellular phagosomes. In contrast, we
show that lysosomes rapidly fuse with the virulent M. tuberculosis-and M. leprae-containing
phagosomes of human monocyte-derived dendritic cells and macrophages. After 2 days, M.
tuberculosis progressively translocates from phagolysosomes into the cytosol in
nonapoptotic cells. Cytosolic entry is also observed for M. leprae but not for vaccine strains …
Summary
M. tuberculosis and M. leprae are considered to be prototypical intracellular pathogens that have evolved strategies to enable growth in the intracellular phagosomes. In contrast, we show that lysosomes rapidly fuse with the virulent M. tuberculosis- and M. leprae-containing phagosomes of human monocyte-derived dendritic cells and macrophages. After 2 days, M. tuberculosis progressively translocates from phagolysosomes into the cytosol in nonapoptotic cells. Cytosolic entry is also observed for M. leprae but not for vaccine strains such as M. bovis BCG or in heat-killed mycobacteria and is dependent upon secretion of the mycobacterial gene products CFP-10 and ESAT-6. The cytosolic bacterial localization and replication are pathogenic features of virulent mycobacteria, causing significant cell death within a week. This may also reveal a mechanism for MHC-based antigen presentation that is lacking in current vaccine strains.
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