Genetic regulation of vesiculogenesis and immunomodulation in Mycobacterium tuberculosis

Proc Natl Acad Sci U S A. 2013 Dec 3;110(49):E4790-7. doi: 10.1073/pnas.1320118110. Epub 2013 Nov 18.

Abstract

Mycobacterium tuberculosis (Mtb) restrains immune responses well enough to escape eradication but elicits enough immunopathology to ensure its transmission. Here we provide evidence that this host-pathogen relationship is regulated in part by a cytosolic, membrane-associated protein with a unique structural fold, encoded by the Mtb gene rv0431. The protein acts by regulating the quantity of Mtb-derived membrane vesicles bearing Toll-like receptor 2 ligands, including the lipoproteins LpqH and SodC. We propose that rv0431 be named "vesiculogenesis and immune response regulator."

Keywords: TLR2; macrophages.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Female
  • Host-Pathogen Interactions
  • Immunomodulation / genetics
  • Immunomodulation / physiology*
  • Lipoproteins / metabolism*
  • Macrophages
  • Magnetic Resonance Spectroscopy
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron, Scanning
  • Models, Molecular*
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / immunology*
  • Protein Folding
  • Toll-Like Receptor 2 / agonists
  • Toll-Like Receptor 2 / genetics
  • Transport Vesicles / metabolism
  • Transport Vesicles / physiology*

Substances

  • Bacterial Proteins
  • Lipoproteins
  • Membrane Proteins
  • Toll-Like Receptor 2

Associated data

  • GEO/GSE50050
  • PDB/2M5Y