Study results from University of Ryukyus provide new insights into pyroptosis
2008 JAN 13 -- "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-1 beta 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)," scientists writing in the journal Plos Pathogens report. "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," wrote T. Suzuki and colleagues, University of Ryukyus. The researchers concluded: "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." Suzuki and colleagues published their study in Plos Pathogens (Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages. Plos Pathogens, 2007;3(8):1082-1091). Additional information can be obtained by contacting T. Suzuki, University of Ryukyus, Graduate School Medical, Division Bacterial Pathogensis, Okinawa, Japan. The publisher of the journal Plos Pathogens can be contacted at: Public Library Science, 185 Berry St., Ste. 1300, San Francisco, CA 94107, USA. Keywords: Japan, Okinawa, Apoptosis, Bacillary Dysentery, Bacterial Infections, Caspase, Cognition, Enzyme Research, Legionella, Legionellosis, Pyroptosis, Salmonella, University of Ryukyus. This article was prepared by Medical Letter on the CDC & FDA editors from staff and other reports. Copyright 2008, Medical Letter on the CDC & FDA via NewsRx.com.
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