Characterization of the Mycobacterium tuberculosis phagosome and evidence that phagosomal maturation is inhibited.

Abstract

We have used the cryosection immunogold technique to study the composition of the Mycobacterium tuberculosis phagosome. We have used quantitative immunogold staining to determine the distribution of several known markers of the endosomal-lysosomal pathway in human monocytes after ingestion of either M. tuberculosis, Legionella pneumophila, or polystyrene beads. Compared with the other phagocytic particles studied, the M. tuberculosis phagosome exhibits delayed clearance of major histocompatibility complex (MHC) class I molecules, relatively intense staining for MHC class II molecules and the endosomal marker transferrin receptor, and relatively weak staining for the lysosomal membrane glycoproteins, CD63, LAMP-1, and LAMP-2 and the lysosomal acid protease, cathepsin D. In contrast to M. tuberculosis, the L. pneumophila phagosome rapidly clears MHC class I molecules and excludes all endosomal-lysosomal markers studied. In contrast to both live M. tuberculosis and L. pneumophila phagosomes, phagosomes containing either polystyrene beads or heat-killed M. tuberculosis stain intensely for lysosomal membrane glycoproteins and cathepsin D. These findings suggest that (a) M. tuberculosis retards the maturation of its phagosome along the endosomal-lysosomal pathway and resides in a compartment with endosomal, as opposed to lysosomal, characteristics; and (b) the intraphagosomal pathway, i.e., the pathway followed by several intracellular parasites that inhibit phagosome-lysosome fusion, is heterogeneous.

• Authors: D L Clemens, M A Horwitz
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 181 Issue 1 Pg. 257-70 (Jan 01 1995) ISSN: 0022-1007 [Print] United States
• PMID: 7807006 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, CD
• CD63 protein, human
• HLA-DR Antigens
• Histocompatibility Antigens Class I
• Lysosome-Associated Membrane Glycoproteins
• Membrane Glycoproteins
• Platelet Membrane Glycoproteins
• Receptors, Transferrin
• Tetraspanin 30
• beta 2-Microglobulin

Topics

• Antigens, CD (metabolism)
• Cell Compartmentation
• HLA-DR Antigens (metabolism)
• Histocompatibility Antigens Class I (metabolism)
• Humans
• Immunohistochemistry
• In Vitro Techniques
• Intracellular Membranes
• Legionella pneumophila (pathogenicity)
• Lysosome-Associated Membrane Glycoproteins
• Lysosomes (physiology)
• Membrane Fusion
• Membrane Glycoproteins (metabolism)
• Monocytes (microbiology)
• Mycobacterium tuberculosis (pathogenicity)
• Phagocytosis
• Phagosomes (physiology, ultrastructure)
• Platelet Membrane Glycoproteins (metabolism)
• Receptors, Transferrin (metabolism)
• Tetraspanin 30
• beta 2-Microglobulin (metabolism)