title: Mycobacterium tuberculosis Rv0652 stimulates production of tumour necrosis factor and monocytes chemoattractant protein-1 in macrophages through the Toll-like receptor 4 pathway.
abstract: Mycobacterial proteins interact with host macrophages and modulate their functions and cytokine gene expression profile. The protein Rv0652 is abundant in culture filtrates of Mycobacterium tuberculosis K-strain, which belongs to the Beijing family, compared with levels in the H37Rv and CDC1551 strains. Rv0652 induces strong antibody responses in patients with active tuberculosis. We investigated pro-inflammatory cytokine production induced by Rv0652 in murine macrophages and the roles of signalling pathways. In RAW264.7 cells and bone marrow-derived macrophages, recombinant Rv0652 induced predominantly tumour necrosis factor (TNF) and monocyte chemoattractant protein (MCP)-1 production, which was dependent on mitogen-activated protein kinases and nuclear factor-κB. Specific signalling pathway inhibitors revealed that the extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and phosphatidylinositol 3-kinase (PI3K) pathways were essential for Rv0652-induced TNF production, whereas the ERK1/2 and PI3K pathways, but not the p38 pathway, were critical for MCP-1 production in macrophages. Rv0652-stimulated TNF and MCP-1 secretion by macrophages occurred in a Toll-like receptor 4-dependent and MyD88-dependent manner. In addition, Rv0652 significantly up-regulated the expression of the mannose receptor, CD80, CD86 and MHC class II molecules. These results suggest that Rv0652 can induce a protective immunity against M. tuberculosis through the macrophage activation.
authors.affiliation: Department of Microbiology and Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, South Korea.
authors.forename: Kwangwook
authors.initials: K
authors.lastname: Kim
authors.forename: Hosung
authors.initials: H
authors.lastname: Sohn
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Kim
authors.forename: Han-Gyu
authors.initials: HG
authors.lastname: Choi
authors.forename: Eui-Hong
authors.initials: EH
authors.lastname: Byun
authors.forename: Kang-In
authors.initials: KI
authors.lastname: Lee
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
authors.forename: Chang-Hwa
authors.initials: CH
authors.lastname: Song
authors.forename: Jeong-Kyu
authors.initials: JK
authors.lastname: Park
authors.forename: Hwa-Jung
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000276:immunology; D005802:Genes, MHC Class II / Q000276:immunology; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000037:antagonists & inhibitors / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D001426:Bacterial Proteins; D018932:Chemokine CCL2; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D011956:Receptors, Cell Surface; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha