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

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.

Intracellular parasitism of parenchymal cells by Mycobacterium leprae

The liver, skeletal muscle, and adrenal gland obtained from two nine-banded armadillos infected with Mycobacterium leprae were studied using an electron microscope. M. leprae were found in varying numbers inside hepatocytes, Kupffer's cells, striated muscle cells, adrenal cortical and adrenal medullary cells, endothelial cells, and macrophages. There was evidence to suggest that M. leprae were actively phagocytosed by the liver and skeletal muscle cells. The inert nature of M. leprae and its behavior as an almost ideal parasite of parenchymal cells are emphasized. The question of whether this unique parasitism of parenchymal cells and the possible processing and presentation of M. leprae antigens by these cells could be responsible for aberrant immune responses is raised

Mycobacterium leprae surface components intervene in the early phagosome-lysosome fusion inhibition event.

Bone marrow-derived cultured macrophages were infected with Mycobacterium leprae. The bacteria were either used as freshly isolated organisms or incubated with M. leprae antiserum (1:5) for 30 min prior to phagocytosis. Immediately after inoculation (1 to 4 h) and at 1 to 8 days later, macrophages were stained for acid phosphatase activity to assess fusions between phagosomes and lysosomes. Inhibition of fusions was essentially apparent as an early event, which was partially reversed by antiserum treatment of the bacteria, suggesting a role for M. leprae immunogenic surface components in this early phenomenon. Later incubation times (1 to 8 days) did not show any considerable difference between antiserum-treated and nontreated bacteria. The formation of an electron-transparent zone around phagocytized bacteria and its role in phagosome-lysosome fusion was investigated, and a direct relationship could not be established.