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Cited by 535

The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.

Differential Regulation of Caspase-1 Activation, Pyroptosis, and Autophagy via Ipaf and ASC in Shigella-Infected Macrophages

Open access
Suzuki, Toshihiko, Franchi, Luigi, Toma, Claudia, Ashida, Hiroshi, Ogawa, Michinaga, Yoshikawa, Yuko, Mimuro, Hitomi, Inohara, Naohiro, Sasakawa, Chihiro, Nuñez, Gabriel·2007·PLoS Pathogens

Abstract

Shigella infection, the cause of bacillary dysentery, induces caspase-1 activation and cell death in macrophages, but the precise mechanisms of this activation remain poorly understood. We demonstrate here 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 was critical for pyroptosis, a specialized form of caspase-1-dependent cell death induced in macrophages by bacterial infection, whereas ASC was dispensable. Unlike that observed in Salmonella and Legionella, caspase-1 activation induced by Shigella infection was independent of flagellin. Notably, infection of macrophages with Shigella induced autophagy, which was dramatically increased by the absence of caspase-1 or Ipaf, but not ASC. Autophagy induced by Shigella required an intact bacterial type III secretion system but not VirG protein, a bacterial factor required for autophagy in epithelial-infected cells. Treatment of macrophages with 3-methyladenine, an inhibitor of autophagy, enhanced pyroptosis induced by Shigella infection, suggesting that autophagy protects infected macrophages from pyroptosis. Thus, Ipaf plays a critical role in caspase-1 activation induced by Shigella independently of flagellin. Furthermore, the absence of Ipaf or caspase-1, but not ASC, regulates pyroptosis and the induction of autophagy in Shigella-infected macrophages, providing a novel function for NLR proteins in bacterial-host interactions.

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Metadata

Authors
Suzuki, T., Franchi, L., Toma, C., Ashida, H., Ogawa, M., Yoshikawa, Y., Mimuro, H., Inohara, N., Sasakawa, C., & Nuñez, G.
Venue
PLoS Pathogens
Published
2007-08-10
Volume
3
Issue
8
Pages
e111
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
OpenAlex
W2054784071
Cited by
535
References
9
FWCI
17.12
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Differential Regulation of Caspase-1 Activation, Pyroptosis, and Autophagy via Ipaf and ASC in Shigella-Infected Macrophages. https://app.cochat.ai/papers/10.1371/journal.ppat.0030111
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Suzuki, T., Franchi, L., Toma, C., Ashida, H., Ogawa, M., Yoshikawa, Y., Mimuro, H., Inohara, N., Sasakawa, C., & Nuñez, G. (2007). Differential Regulation of Caspase-1 Activation, Pyroptosis, and Autophagy via Ipaf and ASC in Shigella-Infected Macrophages. PLoS Pathogens. https://doi.org/10.1371/journal.ppat.0030111

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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