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Toll-like receptor 2-dependent inhibition of macrophage class II MHC expression and antigen processing by 19-kDa lipoprotein of Mycobacterium tuberculosis.
Mycobacterium tuberculosis (MTB) induces vigorous immune responses, yet persists inside macrophages, evading host immunity. MTB bacilli or lysate was found to inhibit macrophage expression of class II MHC (MHC-II) molecules and MHC-II Ag processing. This report characterizes and identifies a specific component of MTB that mediates these inhibitory effects. The inhibitor was extracted from MTB lysate with Triton X-114, isolated by gel electroelution, and identified with Abs to be MTB 19-kDa lipoprotein. Electroelution- or immunoaffinity-purified MTB 19-kDa lipoprotein inhibited MHC-II expression and processing of both soluble Ags and Ag 85B from intact MTB bacilli. Inhibition of MHC-II Ag processing by either MTB bacilli or purified MTB 19-kDa lipoprotein was dependent on Toll-like receptor (TLR) 2 and independent of TLR 4. Synthetic analogs of lipopeptides from Treponema pallidum also inhibited Ag processing. Despite the ability of MTB 19-kDa lipoprotein to activate microbicidal and innate immune functions early in infection, TLR 2-dependent inhibition of MHC-II expression and Ag processing by MTB 19-kDa lipoprotein during later phases of macrophage infection may prevent presentation of MTB Ags and decrease recognition by T cells. This mechanism may allow intracellular MTB to evade immune surveillance and maintain chronic infection.
Authors : Noss E H , Pai R K , Sellati T J , Radolf J D , Belisle J , Golenbock D T , Boom W H , Harding C V ,
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Pathways :
WP2328: Allograft rejection
WP1067: Toll-like receptor signaling pathway
WP1183: Toll-like receptor signaling pathway
WP1271: Toll-like receptor signaling pathway
WP1309: Toll-like receptor signaling pathway
WP1384: Toll-like receptor signaling pathway
WP1449: Regulation of toll-like receptor signaling pathway
WP1963: The effect of Glucocorticoids on target gene expression
WP2272: Pathogenic Escherichia coli infection
WP75: Toll-like receptor signaling pathway
WP829: Toll-like receptor signaling pathway
WP88: Toll Like Receptor signaling
WP949: Toll-like receptor signaling pathway
WP1004: Kit Receptor Signaling Pathway
WP1005: GPCRs, Class B Secretin-like
WP1011: T Cell Receptor Signaling Pathway
WP1014: Androgen receptor signaling pathway
WP1023: mRNA processing
WP1025: B Cell Receptor Signaling Pathway
WP1045: TGF-beta Receptor Signaling Pathway
WP1046: Signaling of Hepatocyte Growth Factor Receptor
WP1051: GPCRs, Class C Metabotropic glutamate, pheromone
WP1072: GPCRs, Class A Rhodopsin-like
WP1112: EPO Receptor Signaling
WP1121: Kit Receptor Signaling Pathway
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Bibliography :
[12816996] Inhibition of IFN-gamma-induced class II transactivator expression by a 19-kDa lipoprotein from Mycobacterium tuberculosis: a potential mechanism for immune evasion.
[11441098] Toll-like receptor 2-dependent inhibition of macrophage class II MHC expression and antigen processing by 19-kDa lipoprotein of Mycobacterium tuberculosis.
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