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Disruption of glycolytic flux is a signal for inflammasome signaling and pyroptotic cell death.


ABSTRACT: When innate immune cells such as macrophages are challenged with environmental stresses or infection by pathogens, they trigger the rapid assembly of multi-protein complexes called inflammasomes that are responsible for initiating pro-inflammatory responses and a form of cell death termed pyroptosis. We describe here the identification of an intracellular trigger of NLRP3-mediated inflammatory signaling, IL-1? production and pyroptosis in primed murine bone marrow-derived macrophages that is mediated by the disruption of glycolytic flux. This signal results from a drop of NADH levels and induction of mitochondrial ROS production and can be rescued by addition of products that restore NADH production. This signal is also important for host-cell response to the intracellular pathogen Salmonella typhimurium, which can disrupt metabolism by uptake of host-cell glucose. These results reveal an important inflammatory signaling network used by immune cells to sense metabolic dysfunction or infection by intracellular pathogens.

SUBMITTER: Sanman LE 

PROVIDER: S-EPMC4846378 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Disruption of glycolytic flux is a signal for inflammasome signaling and pyroptotic cell death.

Sanman Laura E LE   Qian Yu Y   Eisele Nicholas A NA   Ng Tessie M TM   van der Linden Wouter A WA   Monack Denise M DM   Weerapana Eranthie E   Bogyo Matthew M  

eLife 20160324


When innate immune cells such as macrophages are challenged with environmental stresses or infection by pathogens, they trigger the rapid assembly of multi-protein complexes called inflammasomes that are responsible for initiating pro-inflammatory responses and a form of cell death termed pyroptosis. We describe here the identification of an intracellular trigger of NLRP3-mediated inflammatory signaling, IL-1β production and pyroptosis in primed murine bone marrow-derived macrophages that is med  ...[more]

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