Legionella pneumophila down-regulates MHC class I expression of human monocytic host cells and thereby inhibits T cell activation.
Legionella (L.) pneumophila, the causative agent of Legionnaires' disease, is an intracellular pathogen of alveolar macrophages that resides in a compartment displaying features of endoplasmatic reticulum (ER). In this study, we show that intracellular multiplication of L. pneumophila results in a remarkable decrease in MHC class I expression by the infected monocytes. During intracellular multiplication, L. pneumophila absorbs ER-resident chaperons such as calnexin and BiP, molecules that are required for the correct formation of the MHC class I complex. Due to reduced MHC class I expression, stimulation of allogeneic blood mononuclear cells was severely inhibited by infected host cells but cytotoxicity of autologous natural killer cells against Legionella-infected monocytes was not enhanced. Thus, reduced expression of MHC class I in infected monocytes may resemble a new immune escape mechanism induced by L. pneumophila.
Neumeister
B
B
Abteilung Transfusionsmedizin, AG Infektionsbiologie, Universitätsklinikum Tübingen, 72076, Tübingen, Germany. Birgid.Neumeister@med.uni-tuebingen.de
Faigle
M
M
Spitznagel
D
D
Mainka
A
A
Ograbek
A
A
Wieland
H
H
Mannowetz
N
N
Rammensee
H-G
HG
D037281:Calnexin / Q000032:analysis / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000382:microbiology; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D016952:Legionella pneumophila / Q000472:pathogenicity*; D008213:Lymphocyte Activation / Q000276:immunology; D018832:Molecular Chaperones / Q000032:analysis / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology*; D013601:T-Lymphocytes / Q000276:immunology*
D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D018832:Molecular Chaperones; D037281:Calnexin; D007371:Interferon-gamma