Microglia are brain-resident phagocytes with proinflammatory properties and can serve important roles in various neuropathologies. In the EMBO Journal, Outeiro and colleagues investigate whether the NAD+-dependent deacetylase SIRT2 regulates the inflammatory activity of mouse microglia. Intracranial injection of lipopolysaccharide activates microglia, and this is exaggerated after deletion of Sirt2. In vitro culture of microglia cell lines stimulated with lipopolysaccharide (and to some extent, with other ligands of Toll-like receptors) shows that knockdown of Sirt2 enhances the secretion of inflammatory cytokines and release of reactive oxygen and nitrogen species. Cells in which Sirt2 is knocked down also maintain acetylation of the transcription factor NF-κB, which probably accounts for the enhanced transcription of genes encoding inflammatory molecules. Finally, activated microglia in which Sirt2 is knocked down also trigger the death of cocultured primary neurons. Therefore, SIRT2 expressed by microglia seems to be an important anti-inflammatory switch, and defects in its function could contribute to certain diseases of the central nervous system.

EMBO J. (6 September 2013) doi:10.1038/emboj.2013.200