Evidence map›Paper›PMID 17696608›Full record

ArticlePLoS pathogens2007

Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages.

Toshihiko Suzuki, Luigi Franchi, Claudia Toma, Hiroshi Ashida, Michinaga Ogawa, Yuko Yoshikawa, Hitomi Mimuro, Naohiro Inohara, Chihiro Sasakawa, Gabriel Nuñez

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 275 papers.

0numbers the graph read from it
0cells of the map it votes in
275citing papers in PubMed
27.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

275 citing papers in PubMed, 530 citations in OpenAlex.

  1. Article
  2. Article
  3. Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Review
  5. Differential targeting of human pyroptotic Caspase-5 and Caspase-4 bybioRxiv : the preprint server for biology · 2025
    Article
  6. Article
  7. P62 inhibits IL-1β release duringFrontiers in cellular and infection microbiology · 2025
    Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. The Interplay Between Autophagy and Regulated Necrosis.Antioxidants & redox signaling · 2023
    Review
  20. Article

215 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 6 institutions in 2 countries.

Toshihiko SuzukiDivision of Bacterial Pathogenesis, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan. t-suzuki@med.u-ryukyu.ac.jp
Luigi Franchi
Claudia Toma
Hiroshi Ashida
Michinaga Ogawa
Yuko Yoshikawa
Hitomi Mimuro
Naohiro Inohara
Chihiro Sasakawa
Gabriel Nuñez
National Institute of Infectious Diseases · JPUniversity of Michigan–Ann Arbor · USUniversity of the Ryukyus · JPJapan Science and Technology Agency · JPMichigan United · USTokyo University of Science · JP

Funding

Cryopyrin Signaling in Inflammation and Innate ImmunityR01AI063331 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NUNEZ, GABRIEL · 2005 to 2015
$3.3M
Role of Ipaf in Inflammation and Host DefenseR01AI064748 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NUNEZ, GABRIEL · 2005 to 2009
$1.6M
NIAID NIH HHS R01 AI063331NIAID NIH HHS R01 AI064748
6 · The paper itself

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.

Indexed as

Gene Expression Regulation, EnzymologicAdenineAnimalsApoptosisApoptosis Regulatory ProteinsAutophagyBone Marrow CellsCalcium-Binding ProteinsCARD Signaling Adaptor ProteinsCaspase 1Cells, CulturedCytoskeletal ProteinsGene SilencingInterleukin-1betaMacrophagesMice3-methyladenineAdenineApoptosis Regulatory ProteinsCalcium-Binding ProteinsCARD Signaling Adaptor ProteinsCaspase 1Cytoskeletal ProteinsInterleukin-1betaIpaf protein, mousePycard protein, mouse

Identifiers

PMID17696608
PMCPMC1941748
OpenAlexW2054784071

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.