Research ArticleInflammation

Manganese activates NLRP3 inflammasome signaling and propagates exosomal release of ASC in microglial cells

See allHide authors and affiliations

Science Signaling  08 Jan 2019:
Vol. 12, Issue 563, eaat9900
DOI: 10.1126/scisignal.aat9900

Exosomes transfer inflammasome activation

Chronic occupational exposure to manganese is associated with the development of Parkinson’s disease. Sarkar et al. found that exposure of primed microglial cells or mice to manganese increased NLRP3 inflammasome expression and activation. Manganese caused mitochondrial dysfunction in treated microglial cells and stimulated their release of exosomes containing the inflammasome adaptor protein ASC. The effects of manganese on inflammasome activation were sensitive to reduced endocytosis and transferable by exposure of cells to purified exosomes from ASC-sufficient cells. Similarly, serum exosomes from welders contained more ASC and were more inflammatory than those from normal donors, suggesting that occupational manganese exposure may increase systemic inflammasome activation due to exosome-mediated transfer of ASC.