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Mycobacterium tuberculosis Rv0652 stimulates production of tumour necrosis factor and monocytes chemoattractant protein-1 in macrophages through the Toll-like receptor 4 pathway.

 Kwangwook Kim  ;  Hosung Sohn  ;  Jong-Seok Kim  ;  Han-Gyu Choi  ;  Eui-Hong Byun  ;  Kang-In Lee  ;  Sung Jae Shin  ;  Chang-Hwa Song  ;  Jeong-Kyu Park  ;  Hwa-Jung Kim 
 IMMUNOLOGY, Vol.136(2) : 231-240, 2012 
Journal Title
Issue Date
Animals ; B7-1 Antigen/biosynthesis ; B7-1 Antigen/immunology ; B7-2 Antigen/biosynthesis ; B7-2 Antigen/immunology ; Bacterial Proteins/immunology* ; Cell Line ; Chemokine CCL2/biosynthesis* ; Chemokine CCL2/immunology ; Genes, MHC Class II/immunology ; Lectins, C-Type/biosynthesis ; Lectins, C-Type/immunology ; MAP Kinase Signaling System/drug effects ; MAP Kinase Signaling System/immunology ; Macrophage Activation/drug effects ; Macrophage Activation/immunology ; Macrophages/immunology ; Macrophages/metabolism* ; Macrophages/microbiology ; Male ; Mannose-Binding Lectins/biosynthesis ; Mannose-Binding Lectins/immunology ; Mice ; Mice, Inbred C57BL ; Mycobacterium tuberculosis/immunology* ; Myeloid Differentiation Factor 88/antagonists & inhibitors ; Myeloid Differentiation Factor 88/immunology ; NF-kappa B/antagonists & inhibitors ; NF-kappa B/immunology ; Receptors, Cell Surface/biosynthesis ; Receptors, Cell Surface/immunology ; Toll-Like Receptor 4/immunology* ; Tumor Necrosis Factor-alpha/biosynthesis* ; Tumor Necrosis Factor-alpha/immunology
cytokines ; Mycobacterium tuberculosis ; Rv0652 ; macrophage ; signalling
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.
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1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Shin, Sung Jae(신성재) ORCID logo https://orcid.org/0000-0003-0854-4582
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