title: Non-canonical activation of inflammatory caspases by cytosolic LPS in innate immunity.
abstract: Lipopolysaccharide (LPS) is the major component of Gram-negative bacteria cell wall. In innate immunity, extracellular LPS is recognized by Toll-like receptor 4 to stimulate cytokine transcription. Recent studies suggest a 'non-canonical inflammasome' that senses cytoplasmic LPS and activates caspase-11 in mouse macrophages. Unexpectedly, biochemical studies reveal that caspase-11 and its human orthologs caspase-4/caspase-5 are LPS receptors themselves. Direct LPS binding induces caspase-4/caspase-5/caspase-11 oligomerization and activation, triggering cell pyroptosis and anti-bacterial defenses. Caspase-4/caspase-5/caspase-11 recognition of intracellular LPS requires bacterial escape from the vacuole; this process is promoted by interferon-inducible GTPases-mediated lysis of the bacteria-containing vacuole. Non-canonical activation of these inflammatory caspases by LPS not only represents a new paradigm in innate immunity but also critically determines LPS-induced septic shock in mice.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Jieling
authors.initials: J
authors.lastname: Yang
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; National Institute of Biological Sciences, Beijing 102206, China. Electronic address: shaofeng@nibs.ac.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Shao
mesh_terms: D000818:Animals; D020169:Caspases / Q000378:metabolism*; D003600:Cytosol; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D008070:Lipopolysaccharides / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D018805:Sepsis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology
chemical_list: D058847:Inflammasomes; D008070:Lipopolysaccharides; D020169:Caspases