Recombinant Rv1654 protein of Mycobacterium tuberculosis induces mitochondria-mediated apoptosis in macrophage

Microbiol Immunol. 2021 Apr;65(4):178-188. doi: 10.1111/1348-0421.12880. Epub 2021 Mar 24.

Abstract

Mycobacterium tuberculosis contains diverse immunologically active components. This study investigated the biological function of a newly identified component, Rv1654, with the potential to induce apoptosis in macrophages. Recombinant Rv1654 induced macrophage apoptosis in a caspase-9/3-dependent manner through the production of reactive oxygen species (ROS) and interaction with Toll-like receptor 4. In addition, Rv1654 induced the production of tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1 through the mitogen-activated protein kinase pathway. Furthermore, Rv1654-induced c-Jun N-terminal kinase (JNK) activation was inhibited by the ROS scavenger and Rv1654-induced apoptosis was inhibited by the JNK inhibitor. Moreover, it was found that treatment of macrophages with Rv1654 led to the loss of mitochondrial membrane potential, release of cytochrome c into the cytosol, and translocation of Bax into the mitochondria. Finally, Rv1654-mediated apoptosis was inhibited in macrophages transfected with Bax siRNA. These results suggest that Rv1654 induces macrophage apoptosis through a mitochondrial-dependent pathway and ROS-mediated JNK activation.

Keywords: Mycobacterium tuberculosis; RAW264.7 cells; ROS; Rv1654; apoptosis.

MeSH terms

  • Apoptosis*
  • Bacterial Proteins / immunology*
  • Caspases
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Macrophages / metabolism
  • Macrophages / microbiology*
  • Mitochondria*
  • Mycobacterium tuberculosis*
  • Reactive Oxygen Species / metabolism
  • Recombinant Proteins / immunology
  • Toll-Like Receptors

Substances

  • Bacterial Proteins
  • Reactive Oxygen Species
  • Recombinant Proteins
  • Toll-Like Receptors
  • JNK Mitogen-Activated Protein Kinases
  • Caspases