Hypoexpression of major histocompatibility complex molecules on Legionella pneumophila phagosomes and phagolysosomes.
Legionella pneumophila is a facultative intracellular pathogen that parasitizes host mononuclear phagocytes. Cell-mediated immunity is pivotal to host defense against L. pneumophila, and the infected host cell may play a central role in processing and presenting parasite antigens to lymphocytes mediating cell-mediated immune response. However, in the case of L. pneumophila and intracellular parasites in general, little is known about the intracellular trafficking of parasite antigens, the influence of parasite infection on major histocompatibility complex (MHC) expression, or the relationship of MHC molecules to sites of parasite replication. To learn more about this, we have used flow cytometry to study the expression of HLA-DR by monocytes infected with L. pneumophila and cryosection immunogold electron microscopy to study the distribution of MHC class I and II molecules on L. pneumophila phagosomes. Flow cytometry analysis demonstrated that L. pneumophila infection has little effect on the overall expression of HLA-DR by monocytes. Cryosection immunogold studies revealed abundant staining for MHC class I and II molecules on the plasma membrane of infected monocytes but little or no staining on the membranes of mature L. pneumophila phagosomes. Cryosection immunogold studies of an avirulent mutant of L. pneumophila that, unlike the wild type, does not inhibit phagosome-lysosome fusion and subsequently survives but does not multiply in a phagolysosome yielded similar results. We have previously found that MHC class I and II molecules are excluded from nascent phagosomes during coiling and conventional phagocytosis. The present work demonstrates that MHC molecules do not accumulate appreciably in the L. pneumophila phagosome as it matures and at a point in the life cycle of the organism in which it is replicating and producing immunoprotective T-cell antigens. This suggests that L. pneumophila does not reside in a typical endosomal compartment in the host cell and that L. pneumophila antigens may encounter MHC molecules at extraphagosomal sites within the host cell.
Department of Medicine, School of Medicine, University of California, Los Angeles 90024.
D L
DL
Clemens
M A
MA
Horwitz
D000818:Animals; D006684:HLA-DR Antigens / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D016952:Legionella pneumophila / Q000276:immunology*; D051379:Mice; D016253:Microscopy, Immunoelectron; D009000:Monocytes / Q000276:immunology; D010588:Phagosomes / Q000276:immunology*
D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II