The Influence of Mitochondrial-DNA-Driven Inflammation Pathways on Macrophage Polarization: A New Perspective for Targeted Immunometabolic Therapy in Cerebral Ischemia-Reperfusion Injury

Int J Mol Sci. 2021 Dec 23;23(1):135. doi: 10.3390/ijms23010135.

Abstract

Cerebral ischemia-reperfusion injury is related to inflammation driven by free mitochondrial DNA. At the same time, the pro-inflammatory activation of macrophages, that is, polarization in the M1 direction, aggravates the cycle of inflammatory damage. They promote each other and eventually transform macrophages/microglia into neurotoxic macrophages by improving macrophage glycolysis, transforming arginine metabolism, and controlling fatty acid synthesis. Therefore, we propose targeting the mtDNA-driven inflammatory response while controlling the metabolic state of macrophages in brain tissue to reduce the possibility of cerebral ischemia-reperfusion injury.

Keywords: STING; cerebral ischemia-reperfusion; immune metabolism; inflammation; macrophages; mtDNA.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Ischemia / genetics*
  • Cell Polarity / genetics*
  • DNA, Mitochondrial / genetics*
  • Humans
  • Inflammation / genetics*
  • Macrophages / physiology*
  • Reperfusion Injury / genetics*

Substances

  • DNA, Mitochondrial