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

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34 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)231-240
Number of pages10
JournalImmunology
Volume136
Issue number2
DOIs
Publication statusPublished - 2012 Jun 1

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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