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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
Related Genes :
[TLR2 TIL4] Toll-like receptor 2 (Toll/interleukin-1 receptor-like protein 4) (CD antigen CD282)
[TLR1 KIAA0012] Toll-like receptor 1 (Toll/interleukin-1 receptor-like protein) (TIL) (CD antigen CD281)
[Tlr1] Toll-like receptor 1 (Toll/interleukin-1 receptor-like protein) (TIL) (CD antigen CD281)
[TICAM2 TIRAP3 TIRP TRAM] TIR domain-containing adapter molecule 2 (TICAM-2) (Putative NF-kappa-B-activating protein 502) (TRIF-related adapter molecule) (Toll-like receptor adaptor protein 3) (Toll/interleukin-1 receptor domain-containing protein) (MyD88-4)
[Tlr4] Toll-like receptor 4 (Toll4) (CD antigen CD284)
[TLR5 TIL3] Toll-like receptor 5 (Toll/interleukin-1 receptor-like protein 3)
[Toll-7 CG8595] Toll-like receptor 7
[TLR4] Toll-like receptor 4 (hToll) (CD antigen CD284)
[Tlr2] Toll-like receptor 2 (CD antigen CD282)
[TLR6] Toll-like receptor 6 (CD antigen CD286)
[Tlr9] Toll-like receptor 9 (CD antigen CD289)
[TLR9 UNQ5798/PRO19605] Toll-like receptor 9 (CD antigen CD289)
[Tlr4 Lps] Toll-like receptor 4 (CD antigen CD284)
[Tlr6] Toll-like receptor 6 (CD antigen CD286)
[TLR2] Toll-like receptor 2 (CD antigen CD282)
[TLR2] Toll-like receptor 2 (CD antigen CD282)
[TLR6] Toll-like receptor 6 (CD antigen CD286)
[TLR9] Toll-like receptor 9 (CD antigen CD289)
[TLR9] Toll-like receptor 9 (CD antigen CD289)
[TICAM1 PRVTIRB TRIF] TIR domain-containing adapter molecule 1 (TICAM-1) (Proline-rich, vinculin and TIR domain-containing protein B) (Putative NF-kappa-B-activating protein 502H) (Toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta) (MyD88-3) (TIR domain-containing adapter protein inducing IFN-beta)
[TLR8 UNQ249/PRO286] Toll-like receptor 8 (CD antigen CD288)
[TLR7 UNQ248/PRO285] Toll-like receptor 7
[Tlr8] Toll-like receptor 8 (CD antigen CD288)
[TLR4] Toll-like receptor 4 (CD antigen CD284)
[Tlr7] Toll-like receptor 7
[TLR3] Toll-like receptor 3 (CD antigen CD283)
[TIRAP MAL] Toll/interleukin-1 receptor domain-containing adapter protein (TIR domain-containing adapter protein) (Adaptor protein Wyatt) (MyD88 adapter-like protein) (MyD88-2)
[TLR9] Toll-like receptor 9 (CD antigen CD289)
[TLR9] Toll-like receptor 9 (CD antigen CD289)
[Toll-6 Tl-6 CG7250] Toll-like receptor 6
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