期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 16, 页码 6046-6051出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1321700111
关键词
interferon; cell death; immunity-related GTPases; Nos2
资金
- American Heart Association [12PRE10440003]
- National Institutes of Health [R21AI099823, R01AI103197]
- Southeast Regional Center of Excellence for Emerging Infections and Biodefense (SERCEB) [U54-AI-057157]
- Deutsche Forschungsgemeinschaft [FOR729, GRK1045]
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 (Gbp(chr3)). Induction of pyroptosis in naive macrophages by infections with the cytosol-invading.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 Gbp(chr3) proteins. Similarly, pyroptosis induced by cytoplasmic LPS isolated from Salmonella was diminished in Gbp(chr3)-deficient macrophages. These data suggest a role for Gbp(chr3) proteins in the detection of cytoplasmic LPS and the activation of the noncanonical inflammasome.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据