Intersection of group I CD1 molecules and mycobacteria in different intracellular compartments of dendritic cells.
Human CD1a, CD1b, and CD1c molecules can present mycobacterial glycolipids to T cells. Because phagosomes containing viable mycobacteria represent early endosomal compartments, we studied where mycobacterial glycolipids intersect with CD1 molecules in infected APC. CD1b and CD1c, but not CD1a, localized to late endosomes/lysosomes. CD1a and CD1c were predominantly expressed on the cell surface and in mycobacterial phagosomes of the early endosomal stage. In contrast, CD1b was present in a subset of mycobacterial phagosomes representing mature phagolysosomes. Released mycobacterial glycolipids including lipoarabinomannan and phosphatidylinositol mannosides were transported from the phagosome into late endosomes/lysosomes and to uninfected bystander cells. The macrophage mannose receptor, which has been implicated in glycolipid uptake by APC for CD1b-mediated presentation, was absent from mycobacterial phagosomes and may therefore not be involved in trafficking of glycolipids between phagosomes and late endosomes/lysosomes. In conclusion, all three CD1 molecules have access to mycobacteria and glycolipids thereof, but at different intracellular sites. This allows sampling by CD1a, CD1b, and CD1c of mycobacterial glycolipids from different intracellular sites of the infected cell, which has important implications for processing and presentation of such Ags during mycobacterial infections.
Schaible
U E
UE
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany. schaible@mpiib-berlin.mpg.de
Hagens
K
K
Fischer
K
K
Collins
H L
HL
Kaufmann
S H
SH
D018949:Antigens, CD1 / Q000378:metabolism*; D001692:Biological Transport / Q000276:immunology; D002451:Cell Compartmentation / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D011992:Endosomes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D006017:Glycolipids / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology* / Q000382:microbiology*; D037181:Lectins, C-Type; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009163:Mycobacterium bovis / Q000276:immunology* / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism / Q000382:microbiology; D011956:Receptors, Cell Surface / Q000096:biosynthesis
D018949:Antigens, CD1; D006017:Glycolipids; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; C050016:lipoarabinomannan