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

• DOI: 10.1371/journal.ppat.0030111
• Publication Date: 2007-08-08T13:45:02Z
• Authors: Toshihiko Suzuki; Luigi Franchi; Claudia Toma; Hiroshi Ashida; Michinaga Ogawa; Yuko Yoshikawa; Hitomi Mimuro; Naohiro Inohara; Chihiro Sasakawa; Gabriel Nuñez
• Keywords: Pyroptosis

Shigella infection, the cause of bacillary dysentery, induces caspase-1 activation and cell death in macrophages, but precise mechanisms this remain poorly understood. We demonstrate here that IL-1beta processing induced by are mediated through Ipaf, a cytosolic pattern-recognition receptor nucleotide-binding oligomerization domain (NOD)-like (NLR) family, adaptor protein apoptosis-associated speck-like containing C-terminal caspase recruitment (ASC). also show Ipaf was critical for pyroptosis, specialized form caspase-1-dependent macrophages bacterial whereas ASC dispensable. Unlike observed Salmonella Legionella, infection independent flagellin. Notably, with autophagy, which dramatically increased absence or not ASC. Autophagy required an intact type III secretion system VirG protein, factor autophagy epithelial-infected cells. Treatment 3-methyladenine, inhibitor enhanced pyroptosis suggesting protects infected from pyroptosis. Thus, plays role independently Furthermore, caspase-1, ASC, regulates induction Shigella-infected providing novel function NLR proteins bacterial-host interactions.