2024-03-28T19:07:57Z
https://u-ryukyu.repo.nii.ac.jp/oai
oai:u-ryukyu.repo.nii.ac.jp:02011231
2023-08-03T05:31:11Z
1642838163960:1642838338003
1642838403551:1642838407795
Differential Regulation of Caspase-1 Activation, Pyroptosis, and Autophagy via Ipaf and ASC in Shigella-Infected Macrophages
Suzuki, Toshihiko
Franchi, Luigi
Toma, Claudia
Ashida, Hiroshi
Ogawa, Michinaga
Yoshikawa, Yuko
Mimuro, Hitomi
Inohara, Naohiro
Sasakawa, Chihiro
Nunez, Gabriel
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-1β 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.
論文
http://purl.org/coar/resource_type/c_6501
Public Library of Science
2007-08-10
VoR
http://hdl.handle.net/20.500.12000/47240
1553-7366
1553-7374
PLoS Pathogens
8
3
1091
1082
eng
https://doi.org/10.1371/journal.ppat.0030111
https://doi.org/10.1371/journal.ppat.0030111
open access
Creative Commons Attribution 4.0
https://creativecommons.org/licenses/by/4.0/