title: Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin.
abstract: Inflammasomes are cytosolic multiprotein complexes that sense microbial infection and trigger cytokine production and cell death. However, the molecular components of inflammasomes and what they sense remain poorly defined. Here we demonstrate that 35 amino acids of the carboxyl terminus of flagellin triggered inflammasome activation in the absence of bacterial contaminants or secretion systems. To further elucidate the host flagellin-sensing pathway, we generated mice deficient in the intracellular sensor Naip5. These mice failed to activate the inflammasome in response to the 35 amino acids of flagellin or in response to Legionella pneumophila infection. Our data clarify the molecular basis for the cytosolic response to flagellin.
authors: School of Public Health, University of California, Berkeley, CA 94720, USA.
authors: Karla L
authors: KL
authors: Lightfield
authors: Jenny
authors: J
authors: Persson
authors: Sky W
authors: SW
authors: Brubaker
authors: Chelsea E
authors: CE
authors: Witte
authors: Jakob
authors: J
authors: von Moltke
authors: Eric A
authors: EA
authors: Dunipace
authors: Thomas
authors: T
authors: Henry
authors: Yao-Hui
authors: YH
authors: Sun
authors: Dragana
authors: D
authors: Cado
authors: William F
authors: WF
authors: Dietrich
authors: Denise M
authors: DM
authors: Monack
authors: Renée M
authors: RM
authors: Tsolis
authors: Russell E
authors: RE
authors: Vance
mesh_terms: D020816:Amino Acid Motifs / Q000276:immunology; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000276:immunology / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000276:immunology / Q000378:metabolism; D003600:Cytosol; D004797:Enzyme-Linked Immunosorbent Assay; D005408:Flagellin / Q000737:chemistry / Q000276:immunology*; D015151:Immunoblotting; D016952:Legionella pneumophila / Q000276:immunology; D007877:Legionnaires' Disease / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D046912:Multiprotein Complexes / Q000276:immunology*; D051616:Neuronal Apoptosis-Inhibitory Protein / Q000235:genetics / Q000276:immunology*; D051198:Toll-Like Receptor 5 / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; C512299:Ipaf protein, mouse; D046912:Multiprotein Complexes; C496806:Naip5 protein, mouse; D051616:Neuronal Apoptosis-Inhibitory Protein; D051198:Toll-Like Receptor 5; D005408:Flagellin