Acute exercise rewires the proteomic landscape of human immune cells

The positive effect of exercise on the immune system is widely acknowledged, but the molecular response of immune cells to exercise remains largely unknown. Here, we perform mass-spectrometry-based proteomic analysis on peripheral blood mononuclear cells (PBMC) at a depth of >6000 proteins. Comparing high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE), matched for time and workload, we identify versatile changes in the proteomic makeup of PBMCs and reveal profound alterations, related to effector function and immune cell activation pathways within one hour following exercise. These changes are more pronounced after HIIE compared to MICE and occur despite identical immune cell mobilization patterns between the two exercise conditions. We further identify an immunoproteomic signature that effectively predicts cardiorespiratory fitness, thus allowing insights into potential exercise-triggered adaptations and immunological health benefits that are mediated by exercise. This study provides a reliable data resource that expands our knowledge on how exercise modulates the immune system, and delivers biological evidence supporting the WHO 2020 guidelines, which highlight exercise intensity as a relevant factor to maintain health.