Article abstract
Nature Immunology 9, 1171 - 1178 (2008)
Published online: 24 August 2008 | doi:10.1038/ni.1646
Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin
Karla L Lightfield1,7, Jenny Persson2,7, Sky W Brubaker2, Chelsea E Witte3, Jakob von Moltke2, Eric A Dunipace2, Thomas Henry4, Yao-Hui Sun5, Dragana Cado2, William F Dietrich6, Denise M Monack4, Renée M Tsolis5 & Russell E Vance2
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.
- School of Public Health, University of California, Berkeley, California 94720, USA.
- Department of Molecular and Cell Biology, Division of Immunology & Pathogenesis, University of California, Berkeley, California 94720, USA.
- Department of Plant & Microbial Biology, University of California, Berkeley, California 94720, USA.
- Department of Microbiology & Immunology, Stanford University, Stanford, California 94305, USA.
- Department of Medical Microbiology & Immunology, University of California, Davis, California 95616, USA.
- Novartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, USA.
- These authors contributed equally to this work.
Correspondence to: Russell E Vance2 e-mail: rvance@berkeley.edu
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