A role for Nod-like receptors in autophagy induced by Shigella infection

Toshihiko Suzuki1, Gabriel Núñez

  • 1Division of Bacterial Pathogenesis, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan. t-suzuki@med.u-ryukyu.ac.jp

Autophagy
|October 13, 2007
PubMed

Insights

Shigella infection triggers cell death via the Ipaf inflammasome in macrophages. Autophagy, regulated by Ipaf, provides transient resistance to this cell death, revealing a new role for NLR proteins in host defense.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbiology

Background:

  • Shigella infection causes bacillary dysentery, inducing caspase-1 activation and cell death in macrophages.
  • The precise mechanisms of Shigella-induced macrophage cell death remain unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms of Shigella-induced pyroptosis in macrophages.
  • To investigate the role of Ipaf, ASC, and caspase-1 in this process.
  • To explore the relationship between autophagy and pyroptosis during Shigella infection.

Main Methods:

  • Macrophage infection with Shigella.
  • Analysis of caspase-1 activation and IL-1beta processing.
  • Assessment of pyroptosis and autophagy induction.
  • Gene silencing or knockout of Ipaf, ASC, and caspase-1.

Main Results:

  • Shigella-induced caspase-1 activation and IL-1beta processing are mediated by Ipaf and ASC.
  • Ipaf and caspase-1 are essential for pyroptosis, while ASC is dispensable.
  • Shigella infection induces autophagy, which is significantly enhanced in the absence of caspase-1 or Ipaf.
  • Autophagy induction correlates with transient resistance to pyroptosis.

Conclusions:

  • The Ipaf inflammasome is a key regulator of Shigella-induced pyroptosis in macrophages.
  • Autophagy is regulated by the Ipaf inflammasome and confers transient resistance to pyroptosis.
  • NLR proteins play a novel role in modulating bacterial-host interactions through the regulation of autophagy and cell death pathways.

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