A role for Nod-like receptors in autophagy induced by Shigella infection |
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Authors: | Suzuki Toshihiko Núñez Gabriel |
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Institution: | Division of Bacterial Pathogenesis, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan. t-suzuki@med.u-ryukyu.ac.jp |
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Abstract: | Shigella infection, the cause of bacillary dysentery, induces caspase-1 activation and cell death in macrophages, but the precise mechanisms remain poorly understood. In our recent study, we presented evidence 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 and caspase-1 were critical for pyroptosis, a specialized form of caspase-1-dependent cell death induced in macrophages by bacterial infection, whereas ASC is dispensable. Notably, infection of macrophages with Shigella induced autophagy, which was dramatically increased by the absence of caspase-1 or Ipaf, but not ASC. Furthermore, autophagy induction was associated with transient resistance to pyroptosis. These results indicate that autophagy in macrophages is regulated by the Ipaf inflammasome, providing a novel function for NLR proteins in bacterial-host interactions. |
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