Moderate exercise induces trained immunity in macrophages

Despite its importance in protecting the host from infections and injury, excessive inflammation may lead to serious human diseases including autoimmune disorders, cardiovascular diseases, diabetes, and cancer. Exercise is a known immunomodulator; however, whether exercise causes long-term changes in inflammatory responses and how these changes occur are lacking. Here, we show that chronic moderate-intensity training of mice leads to persistent metabolic rewiring and changes to chromatin accessibility in bone marrow-derived macrophages (BMDMs), which, in turn, tempers their inflammatory responses. We show that BMDMs from exercised mice exhibited a decrease in lipopolysaccharide (LPS)-induced NF -KB activation and proinflammatory gene expression along with an increase in M2-like-associated genes when compared with BMDMs from sedentary mice. This was associated with improved mitochondrial quality and increased reliance on oxidative phosphorylation accompanied with reduced mitochondrial reactive oxygen species (ROS) production. Mechanistically, assay for transposase-accessible chromatin (ATAC)-seq analysis showed changes in chromatin accessibility of genes associated with inflammatory and metabolic pathways. Overall, our data suggest that chronic moderate exercise can influence the inflammatory responses of macrophages by reprogramming their metabolic and epigenetic landscape.

Automated summary

Exercise can modify the metabolism and epigenetic genome of bone marrow-derived macrophages (BMDMs), leading to suppression of inflammatory responses. The study found that chronic moderate training can decrease NF-κB activation and proinflammatory gene expression in BMDMs stimulated with bacterial components, while increasing the expression of M2-like-associated genes. This is accompanied by improved mitochondrial quality and reduced production of reactive oxygen species. These findings suggest that exercise influences the inflammatory responses of macrophages by reprogramming their metabolism and epigenetic genome.