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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.

SUBMITTER: Lightfield KL

PROVIDER: S-EPMC2614210 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin.

Lightfield Karla L KL Persson Jenny J Brubaker Sky W SW Witte Chelsea E CE von Moltke Jakob J Dunipace Eric A EA Henry Thomas T Sun Yao-Hui YH Cado Dragana D Dietrich William F WF Monack Denise M DM Tsolis Renée M RM Vance Russell E RE

Nature immunology 20080824 10

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 intracell ...[more]

PMID: 18724372

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