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Immunoresponsive Gene 1 Augments Bactericidal Activity of Macrophage-Lineage Cells by Regulating β-Oxidation-Dependent Mitochondrial ROS Production.
- Source :
- Cell Metabolism; Aug2013, Vol. 18 Issue 2, p265-278, 14p
- Publication Year :
- 2013
-
Abstract
- Summary: Evidence suggests the bactericidal activity of mitochondria-derived reactive oxygen species (mROS) directly contributes to killing phagocytozed bacteria. Infection-responsive components that regulate this process remain incompletely understood. We describe a role for the mitochondria-localizing enzyme encoded by Immunoresponsive gene 1 (IRG1) during the utilization of fatty acids as a fuel for oxidative phosphorylation (OXPHOS) and associated mROS production. In a zebrafish infection model, infection-responsive expression of zebrafish irg1 is specific to macrophage-lineage cells and is regulated cooperatively by glucocorticoid and JAK/STAT signaling pathways. Irg1-depleted macrophage-lineage cells are impaired in their ability to utilize fatty acids as an energy substrate for OXPHOS-derived mROS production resulting in defective bactericidal activity. Additionally, the requirement for fatty acid β-oxidation during infection-responsive mROS production and bactericidal activity toward intracellular bacteria is conserved in murine macrophages. These results reveal IRG1 as a key component of the immunometabolism axis, connecting infection, cellular metabolism, and macrophage effector function. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 15504131
- Volume :
- 18
- Issue :
- 2
- Database :
- Supplemental Index
- Journal :
- Cell Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 89608157
- Full Text :
- https://doi.org/10.1016/j.cmet.2013.06.018