Moderate exercise induces trained immunity in macrophages.

Area of Science:

• Immunology
• Exercise Physiology
• Epigenetics

Background:

• Excessive inflammation contributes to chronic diseases like autoimmune disorders, cardiovascular disease, diabetes, and cancer.
• Exercise is a known immunomodulator, but long-term effects on inflammatory responses and their mechanisms are not fully understood.

Purpose of the Study:

• To investigate how chronic moderate exercise training impacts inflammatory responses in macrophages.
• To elucidate the underlying metabolic and epigenetic mechanisms responsible for exercise-induced immunomodulation.

Main Methods:

• Chronic moderate-intensity exercise training in mice.
• Analysis of bone marrow-derived macrophages (BMDMs) for inflammatory gene expression and NF-κB activation.
• Assay for transposase-accessible chromatin (ATAC)-seq to assess chromatin accessibility.
• Mitochondrial function assessment, including reactive oxygen species (ROS) production and oxidative phosphorylation.

Main Results:

• Exercised mice exhibited reduced lipopolysaccharide (LPS)-induced NF-κB activation and pro-inflammatory gene expression in BMDMs.
• BMDMs from exercised mice showed increased M2-like gene expression.
• Improved mitochondrial quality, enhanced oxidative phosphorylation, and reduced ROS production were observed in BMDMs from exercised mice.
• ATAC-seq revealed altered chromatin accessibility in genes related to inflammatory and metabolic pathways.

Conclusions:

• Chronic moderate exercise induces persistent metabolic and epigenetic reprogramming in macrophages.
• This reprogramming tempers inflammatory responses by altering gene expression and improving mitochondrial function.
• Exercise influences macrophage inflammatory responses through metabolic and epigenetic landscape modifications.