Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acyltransferases*
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Animals
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Antigen Presentation / genetics
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Antigen Presentation / immunology*
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Antigens, Bacterial*
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Bacterial Proteins / antagonists & inhibitors
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Bacterial Proteins / isolation & purification
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Bacterial Proteins / metabolism
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Bacterial Proteins / pharmacology*
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Detergents
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Drosophila Proteins*
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Epitopes / metabolism
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Female
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Histocompatibility Antigens Class II / biosynthesis*
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Histocompatibility Antigens Class II / immunology
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Histocompatibility Antigens Class II / metabolism
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Immunosuppressive Agents / pharmacology*
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Lipoproteins / pharmacology*
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Macrophages / immunology*
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Macrophages / metabolism
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Macrophages / microbiology
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Knockout
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Mycobacterium tuberculosis / immunology*
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Octoxynol
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Polyethylene Glycols
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Receptors, Cell Surface / deficiency
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / physiology*
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Toll-Like Receptor 2
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Toll-Like Receptor 4
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Toll-Like Receptors
Substances
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19 kDa antigen, Mycobacterium
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Antigens, Bacterial
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Bacterial Proteins
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Detergents
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Drosophila Proteins
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Epitopes
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Histocompatibility Antigens Class II
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Immunosuppressive Agents
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Lipoproteins
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Membrane Glycoproteins
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Receptors, Cell Surface
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Toll-Like Receptor 2
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Toll-Like Receptor 4
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Toll-Like Receptors
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Polyethylene Glycols
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Octoxynol
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Nonidet P-40
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Acyltransferases
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antigen 85B, Mycobacterium tuberculosis