Toll-like Receptor 2-dependent Inhibition of Macrophage Class II MHC Expression and Antigen Processing by 19-kDa Lipoprotein of Mycobacterium Tuberculosis

J Immunol. 2001 Jul 15;167(2):910-8. doi: 10.4049/jimmunol.167.2.910.

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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyltransferases*
  • Animals
  • Antigen Presentation / genetics
  • Antigen Presentation / immunology*
  • Antigens, Bacterial*
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / isolation & purification
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / pharmacology*
  • Detergents
  • Drosophila Proteins*
  • Epitopes / metabolism
  • Female
  • Histocompatibility Antigens Class II / biosynthesis*
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism
  • Immunosuppressive Agents / pharmacology*
  • Lipoproteins / pharmacology*
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mycobacterium tuberculosis / immunology*
  • Polyethylene Glycols
  • Receptors, Cell Surface / deficiency
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology*
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors

Substances

  • 19 kDa antigen, Mycobacterium
  • Antigens, Bacterial
  • Bacterial Proteins
  • Detergents
  • Drosophila Proteins
  • Epitopes
  • Histocompatibility Antigens Class II
  • Immunosuppressive Agents
  • Lipoproteins
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Polyethylene Glycols
  • Nonidet P-40
  • Acyltransferases
  • antigen 85B, Mycobacterium tuberculosis