Mce-associated protein Rv0177 alters the cell wall structure of Mycobacterium smegmatis and promotes macrophage apoptosis via regulating the cytokines

Int Immunopharmacol. 2019 Jan:66:205-214. doi: 10.1016/j.intimp.2018.11.013. Epub 2018 Nov 22.

Abstract

The success of Mycobacterium tuberculosis as a pathogen largely contributes to its ability to infect, modify and persist within the host cells. M. tuberculosis Rv0177 is a gene of the mce1 operon (Mammalian cell entry), encoding a conserved hypothetical protein, essential for M. tuberculosis survival and up-regulated within murine macrophages. To explore its function, Rv0177 was heterologously expressed in M. smegmatis. The recombinant protein was located in the cell wall. M. smegmatis recombinant strain expressing Rv0177 altered sliding motility, its cell wall architecture and the permeability. Moreover, M. smegmatis expressing Rv0177 could up-regulate MCP-1 and downregulate the IL-6 expression in RAW264.7 macrophages in comparison to the control. MS_Rv0177 increased the expression of MCP-1 inducible protein (MCPIP) and a C/EBP homologous protein (CHOP) owing to MCP-1. In addition, the JNK signaling pathway was engaged in the interplay between MS_Rv0177 and macrophages. The macrophage caspase-3 activation and cell apoptosis were induced by the recombinant. This provided novel functional cues for the MCE-associated Rv0177.

Keywords: Apoptosis; Cytokines; Endoplasmic reticulum stress; Mycobacterium tuberculosis; Rv0177.

MeSH terms

  • Animals
  • Apoptosis
  • Bacterial Adhesion / genetics
  • Bacterial Proteins / genetics*
  • Caspase 3 / metabolism
  • Cell Movement / genetics
  • Cell Wall / physiology*
  • Chemokine CCL2 / metabolism
  • Cytokines / metabolism
  • MAP Kinase Signaling System
  • Macrophages / microbiology
  • Macrophages / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Microorganisms, Genetically-Modified
  • Mycobacterium smegmatis / physiology*
  • Mycobacterium tuberculosis / physiology*
  • RAW 264.7 Cells
  • Tuberculosis / immunology
  • Tuberculosis / microbiology*

Substances

  • Bacterial Proteins
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Cytokines
  • mammalian cell entry protein Mce1A, Mycobacterium tuberculosis
  • Caspase 3