Critical Function for Naip5 in Inflammasome Activation by a Conserved Carboxy-Terminal Domain of Flagellin

Nat Immunol. 2008 Oct;9(10):1171-8. doi: 10.1038/ni.1646. Epub 2008 Aug 24.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / immunology
  • Animals
  • Apoptosis Regulatory Proteins / immunology
  • Apoptosis Regulatory Proteins / metabolism
  • Calcium-Binding Proteins / immunology
  • Calcium-Binding Proteins / metabolism
  • Cytosol
  • Enzyme-Linked Immunosorbent Assay
  • Flagellin / chemistry
  • Flagellin / immunology*
  • Immunoblotting
  • Legionella pneumophila / immunology
  • Legionnaires' Disease / immunology
  • Macrophages / immunology*
  • Macrophages / microbiology
  • Mice
  • Multiprotein Complexes / immunology*
  • Neuronal Apoptosis-Inhibitory Protein / genetics
  • Neuronal Apoptosis-Inhibitory Protein / immunology*
  • Toll-Like Receptor 5 / immunology
  • Toll-Like Receptor 5 / metabolism
  • Transduction, Genetic

Substances

  • Apoptosis Regulatory Proteins
  • Calcium-Binding Proteins
  • Ipaf protein, mouse
  • Multiprotein Complexes
  • Naip5 protein, mouse
  • Neuronal Apoptosis-Inhibitory Protein
  • Toll-Like Receptor 5
  • Flagellin