Interaction of Mycobacterium avium-containing phagosomes with the antigen presentation pathway.
Pathogenic mycobacteria infect macrophages where they replicate in phagosomes that minimize contact with late endosomal/lysosomal compartments. Loading of Ags to MHC class II molecules occurs in specialized compartments with late endosomal characteristics. This points to a sequestration of mycobacteria-containing phagosomes from the sites where Ags meet MHC class II molecules. Indeed, in resting macrophages MHC class II levels decreased strongly in phagosomes containing M. avium during a 4-day infection. Phagosomal MHC class II of early (4 h) infections was partly surface-derived and associated with peptide. Activation of host macrophages led to the appearance of H2-M, a chaperon of Ag loading, and to a strong increase in MHC class II molecules in phagosomes of acute (1 day) infections. Comparison with the kinetics of MHC class II acquisition by IgG-coated bead-containing phagosomes suggests that the arrest in phagosome maturation by mycobacteria limits the intersection of mycobacteria-containing phagosomes with the intracellular trafficking pathways of Ag-presenting molecules.
Ullrich
H J
HJ
College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. Department of Microbiology, Washington University, St. Louis, MO 63110, USA. hu23@cornell.edu
Beatty
W L
WL
Russell
D G
DG
D000818:Animals; D017951:Antigen Presentation; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002451:Cell Compartmentation / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002478:Cells, Cultured; D006681:HLA-D Antigens / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008262:Macrophage Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D009162:Mycobacterium avium / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D010587:Phagocytosis / Q000276:immunology; D010588:Phagosomes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*
C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II