Recombinant MPT83 derived from Mycobacterium tuberculosis induces cytokine production and upregulates the function of mouse macrophages through TLR2

J Immunol. 2012 Jan 15;188(2):668-77. doi: 10.4049/jimmunol.1102177. Epub 2011 Dec 14.


TLR2 recognizes components of Mycobacterium tuberculosis and initiates APC activities that influence both innate and adaptive immunity. M. tuberculosis lipoproteins are an important class of TLR2 ligands. In this study, we focused on recombinant MPT83 (rMPT83) to determine its effects on mouse macrophages. We demonstrated that rMPT83 induced the production of TNF-α, IL-6, and IL-12 p40 and that cytokine induction depended on activated MAPKs, because we observed the rapid phosphorylation of ERK1/2, p38, and JNK in macrophages. Additionally, neutralizing Abs against TLR2 significantly inhibited cytokine secretion and reduced or attenuated the rMPT83-induced activation of p38 and JNK in RAW264.7 cells, a mouse macrophage cell line. Furthermore, rMPT83-induced cytokine production was significantly lower in macrophages from TLR2(-/-) mice than in macrophages from wild-type mice. We further found that prolonged exposure (>24 h) of RAW264.7 cells or macrophages from wild-type and TLR2(-/-) mice to rMPT83 resulted in a significant enhancement of IFN-γ-induced MHC class II expression and an enhanced ability of macrophages to present the rMPT83 peptide to CD4(+) T cells. These results indicated that rMPT83 is a TLR2 agonist that induces the production of cytokines by macrophages and upregulates macrophage function.

MeSH terms

  • Animals
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / physiology*
  • Bacterial Proteins / agonists
  • Bacterial Proteins / genetics
  • Bacterial Proteins / physiology*
  • Cell Line
  • Cytokines / biosynthesis*
  • HEK293 Cells
  • Humans
  • Interleukin-12 Subunit p40 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Macrophages, Peritoneal / immunology*
  • Macrophages, Peritoneal / metabolism*
  • Membrane Proteins / agonists
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Recombinant Proteins / agonists
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology
  • Toll-Like Receptor 2 / deficiency
  • Toll-Like Receptor 2 / physiology*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Up-Regulation / immunology*


  • Antigens, Bacterial
  • Bacterial Proteins
  • Cytokines
  • Interleukin-12 Subunit p40
  • Interleukin-6
  • MPB83 protein, Mycobacterium
  • Membrane Proteins
  • Recombinant Proteins
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Tumor Necrosis Factor-alpha