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The Mycobacterium tuberculosis Phagosome Interacts with Early Endosomes and Is Accessible to Exogenously Administered Transferrin

The Mycobacterium tuberculosis Phagosome Interacts with Early Endosomes and Is Accessible to Exogenously Administered Transferrin,Daniel L. Clemens,Ma

The Mycobacterium tuberculosis Phagosome Interacts with Early Endosomes and Is Accessible to Exogenously Administered Transferrin   (Citations: 60)
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Summary Previous studies have demonstrated that the Mycobacterium tuberculosis phagosome in human monocyte-derived macrophages acquires markers of early and late endosomes, but direct evi- dence 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. tuber- culosis phagosome acquires exogenously added transferrin in a time-dependent fashion. Near- maximal acquisition of transferrin occurs within 15 rain, 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. ~p Obacterium tuberculosis is an intracellular pathogen that arasitizes human mononuclear phagocytes. Through- out its life cycle in these host cells, this bacterium resides and multiplies in a membrane-bound phagosome that re- sists acidification and fusion with lysosomes (1-4). In previ- ous studies, using quantitative immunoelectron microscopy, we have examined the composition and maturation of the M. tuberculosis phagosome, focusing on known markers of the endocytic pathway (4). These studies revealed that the M. tuberculosis phagosome exhibits delayed clearance of MHC class I molecules, relatively intense staining for MHC class II molecules and the endosomal marker transfemn recep- tor, and relatively weak staining for the lysosome-associated membrane glycoproteins CD63, LAMP-l, and LAMP-2 and the lysosomal acid protease cathepsin D. Like M. tuber- culosis, wild-type Legionella pneumophila inhibits phagosome- lysosome fusion and phagosome acidification (5, 6). How- ever, in contrast to the M. tuberculosis phagosome, the L.
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    • ...-containing phagosomes fuse with early endosomes but are unable to fuse with late endosomes ...

    Eric Ghigoet al. IL16 Promotes T. whipplei Replication by Inhibiting Phagosome Conversi...

    • ...The mycobacterial phagosome retains the early endosomal GTPase rab5 (Clemens et al., 2000; Kelley & Schorey, 2003; Via et al., 1997) and access to transferrin within the rapid recycling pathway (Clemens & Horwitz, 1996; Sturgill-Koszycki et al., 1996)...

    Silvana K. Rampiniet al. LspA inactivation in Mycobacterium tuberculosis results in attenuation...

    • ...Conversely, feeding inside vesicles may sound more difficult but might not be so. Vesicles harboring parasites may fuse with other vesicular compartments and thus, acquire nutrients: The endosomal route may bring iron in the form of holo-transferrin [95], and it is not unlikely that other nutrients may be transported through this organelle; fusion with other intracellular membrane systems has been described, such as with the ER [25], where ...
    • ...M. tuberculosis dwells in endosomal compartments with access to transferrin and thus to iron [95]...

    Rui Appelberg. Macrophage nutriprive antimicrobial mechanisms

    • ...Transferrin receptors are synthesized in the host cell endoplasmic reticulum and transported to the host cell surface, where they bind to transferrin and the receptor-ligand complexes are internalized in early endosomes (15)...

    Yongqun Heet al. Brucella melitensis Triggers Time-Dependent Modulation of Apoptosis an...

    • ...Extracellular Tf traffics to M.tb-containing phagosomes through plasma membrane transferrin receptor (TfR) cycling to early endosomes [13, 14]...
    • ...The M.tb phagosome interacts with early endosomes and is accessible to exogenously administered Tf [13]...
    • ...It has been proposed that this provides M.tb with Fe [13]...
    • ...M.tb phagosome in macrophages [13, 14], purportedly as a result of movement of Tf/TfR complex-containing early endosomes to M.tb containing phagosomes...
    • ...Tf has been shown to move to M.tb-containing macrophage phagosomes [13, 14]...

    Oyebode Olakanmiet al. Hereditary hemochromatosis results in decreased iron acquisition and g...

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