Mycobacterium tuberculosis evades macrophage defenses by inhibiting plasma membrane repair

Nat Immunol. 2009 Aug;10(8):899-906. doi: 10.1038/ni.1758. Epub 2009 Jun 28.


Induction of macrophage necrosis is a strategy used by virulent Mycobacterium tuberculosis (Mtb) to avoid innate host defense. In contrast, attenuated Mtb causes apoptosis, which limits bacterial replication and promotes T cell cross-priming by antigen-presenting cells. Here we show that Mtb infection causes plasma membrane microdisruptions. Resealing of these lesions, a process crucial for preventing necrosis and promoting apoptosis, required translocation of lysosomal and Golgi apparatus-derived vesicles to the plasma membrane. Plasma membrane repair depended on prostaglandin E(2) (PGE(2)), which regulates synaptotagmin 7 (Syt-7), the calcium sensor involved in the lysosome-mediated repair mechanism. By inducing production of lipoxin A(4) (LXA(4)), which blocks PGE(2) biosynthesis, virulent Mtb prevented membrane repair and induced necrosis. Thus, virulent Mtb impairs macrophage plasma membrane repair to evade host defenses.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cell Membrane / pathology*
  • Cell Membrane Permeability
  • Cells, Cultured
  • Dinoprostone / metabolism
  • Golgi Apparatus / physiology
  • Humans
  • Lipoxins / metabolism
  • Lysosomes / physiology
  • Macrophages / immunology
  • Macrophages / microbiology*
  • Macrophages / pathology
  • Mice
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / pathogenicity
  • Mycobacterium tuberculosis / physiology*
  • Necrosis
  • Synaptotagmins / metabolism
  • Virulence


  • Lipoxins
  • Syt7 protein, mouse
  • lipoxin A4
  • Synaptotagmins
  • Dinoprostone