Mycobacterium tuberculosis PE_PGRS18 enhances the intracellular survival of M. smegmatis via altering host macrophage cytokine profiling and attenuating the cell apoptosis

Apoptosis. 2017 Apr;22(4):502-509. doi: 10.1007/s10495-016-1336-0.

Abstract

Mycobacterium tuberculosis PE/PPE family proteins, named after the presence of conserved PE (Pro-Glu) and PPE (Pro-Pro-Glu) domains at N-terminal, are prevalent in M. tuberculosis genome. The function of most PE/PPE family proteins remains elusive. To characterize the function of PE_PGRS18, the encoding gene was heterologously expressed in M. smegmatis, a nonpathogenic mycobacterium. The recombinant PE_PGRS18 is cell wall associated. M. smegmatis PE_PGRS18 recombinant showed differential response to stresses and altered the production of host cytokines IL-6, IL-1β, IL-12p40 and IL-10, as well as enhanced survival within macrophages largely via attenuating the apoptosis of macrophages. In summary, the study firstly unveiled the role of PE_PGRS18 in physiology and pathogenesis of mycobacterium.

Keywords: Apoptosis; Cytokine; Mycobacterium tuberculosis; PE-PGRS family; PE_PGRS 18.

MeSH terms

  • Animals
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / physiology*
  • Apoptosis / physiology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / physiology*
  • Cytokines / biosynthesis*
  • Genes, Bacterial
  • Humans
  • Macrophages / metabolism
  • Macrophages / microbiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mycobacterium smegmatis / cytology
  • Mycobacterium smegmatis / physiology*
  • Mycobacterium tuberculosis / cytology
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / physiology*
  • Nitric Oxide / metabolism
  • Protein Domains
  • Recombinant Fusion Proteins / metabolism
  • THP-1 Cells
  • Up-Regulation

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Cytokines
  • Membrane Proteins
  • PE-PGRS protein, Mycobacterium
  • PE_PGRS18 protein, Mycobacterium tuberculosis
  • Recombinant Fusion Proteins
  • Nitric Oxide