title: Toll-like receptor 2-dependent inhibition of macrophage class II MHC expression and antigen processing by 19-kDa lipoprotein of Mycobacterium tuberculosis.
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.
authors: Department of Pathology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA.
authors: E H
authors: EH
authors: Noss
authors: R K
authors: RK
authors: Pai
authors: T J
authors: TJ
authors: Sellati
authors: J D
authors: JD
authors: Radolf
authors: J
authors: J
authors: Belisle
authors: D T
authors: DT
authors: Golenbock
authors: W H
authors: WH
authors: Boom
authors: C V
authors: CV
authors: Harding
mesh_terms: D000217:Acyltransferases; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D003902:Detergents; D029721:Drosophila Proteins; D000939:Epitopes / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008074:Lipoproteins / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D017830:Octoxynol; D011092:Polyethylene Glycols; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: C087864:19 kDa antigen, Mycobacterium; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D003902:Detergents; D029721:Drosophila Proteins; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D011092:Polyethylene Glycols; D017830:Octoxynol; C010615:Nonidet P-40; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis