| First Author | Sanman LE | Year | 2016 |
| Journal | Elife | Volume | 5 |
| Pages | e13663 | PubMed ID | 27011353 |
| Mgi Jnum | J:269692 | Mgi Id | MGI:6204373 |
| Doi | 10.7554/eLife.13663 | Citation | Sanman LE, et al. (2016) Disruption of glycolytic flux is a signal for inflammasome signaling and pyroptotic cell death. Elife 5:e13663 |
| abstractText | 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-1beta 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. |
