期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2014
卷号：111
期号：16
页码：6046-6051
DOI：10.1073/pnas.1321700111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：IFN receptor signaling induces cell-autonomous immunity to infections with intracellular bacterial pathogens. Here, we demonstrate that IFN-inducible guanylate binding protein (Gbp) proteins stimulate caspase-11-dependent, cell-autonomous immunity in response to cytoplasmic LPS. Caspase-11-dependent pyroptosis is triggered in IFN-activated macrophages infected with the Gram-negative bacterial pathogen Legionella pneumophila. The rapid induction of pyroptosis in IFN-activated macrophages required a cluster of IFN-inducible Gbp proteins encoded on mouse chromosome 3 (Gbpchr3). Induction of pyroptosis in naive macrophages by infections with the cytosol-invading {Delta}sdhA L. pneumophila mutant was similarly dependent on Gbpchr3, suggesting that these Gbp proteins play a role in the detection of bacteria accessing the cytosol. Cytoplasmic LPS derived from Salmonella ssp. or Escherichia coli has recently been shown to trigger caspase-11 activation and pyroptosis, but the cytoplasmic sensor for LPS and components of the caspase-11 inflammasome are not yet defined. We found that the induction of caspase-11-dependent pyroptosis by cytoplasmic L. pneumophila-derived LPS required Gbpchr3 proteins. Similarly, pyroptosis induced by cytoplasmic LPS isolated from Salmonella was diminished in Gbpchr3-deficient macrophages. These data suggest a role for Gbpchr3 proteins in the detection of cytoplasmic LPS and the activation of the noncanonical inflammasome.
关键词：interferon ; cell death ; immunity-related GTPases ; Nos2
