Human IRGM induces autophagy to eliminate intracellular mycobacteria

Science. 2006 Sep 8;313(5792):1438-41. doi: 10.1126/science.1129577. Epub 2006 Aug 3.

Abstract

Immunity-related p47 guanosine triphosphatases (IRG) play a role in defense against intracellular pathogens. We found that the murine Irgm1 (LRG-47) guanosine triphosphatase induced autophagy and generated large autolysosomal organelles as a mechanism for the elimination of intracellular Mycobacterium tuberculosis. We also identified a function for a human IRG protein in the control of intracellular pathogens and report that the human Irgm1 ortholog, IRGM, plays a role in autophagy and in the reduction of intracellular bacillary load.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autophagy*
  • Cell Line
  • Cytosol / metabolism
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / physiology*
  • HeLa Cells
  • Humans
  • Interferon-gamma / immunology
  • Lysosomes / metabolism
  • Lysosomes / microbiology
  • Lysosomes / ultrastructure
  • Macrophages / immunology*
  • Macrophages / microbiology*
  • Mice
  • Microbial Viability
  • Microtubule-Associated Proteins / metabolism
  • Mycobacterium bovis / immunology*
  • Mycobacterium bovis / physiology
  • Phagosomes / metabolism
  • Phagosomes / microbiology
  • Phagosomes / ultrastructure*
  • RNA, Small Interfering
  • Transfection
  • Vacuoles / metabolism
  • Vacuoles / ultrastructure

Substances

  • Ifi1 protein, mouse
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • RNA, Small Interfering
  • Interferon-gamma
  • GTP-Binding Proteins
  • IRGM protein, human