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Updated: Jul 10, 2026

Use of Shigella flexneri to Study Autophagy-Cytoskeleton Interactions
Published on: September 9, 2014
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
Abstract:
Shigella infection, the cause of bacillary dysentery, induces caspase-1 activation and cell death in macrophages, but the precise mechanisms remain poorly understood. In our recent study, we presented evidence that caspase-1 activation and IL-1beta processing induced by Shigella are mediated through Ipaf, a cytosolic pattern-recognition receptor of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family and the adaptor protein apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC). We also show that Ipaf and caspase-1 were critical for pyroptosis, a specialized form of caspase-1-dependent cell death induced in macrophages by bacterial infection, whereas ASC is dispensable. Notably, infection of macrophages with Shigella induced autophagy, which was dramatically increased by the absence of caspase-1 or Ipaf, but not ASC. Furthermore, autophagy induction was associated with transient resistance to pyroptosis. These results indicate that autophagy in macrophages is regulated by the Ipaf inflammasome, providing a novel function for NLR proteins in bacterial-host interactions.
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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