Western lifestyle linked to maladaptive trained immunity
- Institute of Innate Immunity, University Hospital Bonn, Germany
- Deutsches Rheuma-Forschungszentrum (DRFZ), Germany
Figures
Figure 1
Maladaptive trained immunity (TI) leads to a heightened inflammatory response and exacerbated disease outcomes.
Using murine models, different triggers have been identified, and studies using bone marrow transplantation show that central reprogramming within the bone marrow is pivotal for maladaptive TI. These experiments demonstrate that long-lasting epigenetic and metabolic changes in HSPCs drive persistently heightened inflammatory responses and as such contribute to chronic, dysregulated inflammation. In humans, evidence remains scarcer, yet multiple lifestyle factors, as well as established risk factors for chronic inflammatory diseases, have been proposed as potential triggers of maladaptive TI. These factors are known to enhance systemic inflammation and may similarly imprint long-term changes on immune cells.
Tables
Table 1
Suggested lifestyle interventions to prevent or reduce maladaptive TI-related inflammation.
| Lifestyle modulation | Disease type | Cellular and molecular targets | Possible off-target effects | References |
|---|---|---|---|---|
| Dietary and weight management, alcohol moderation | Gout | Reduction of uric acid prevents crystal formation in the joints | Nutrient deficiencies | Zhang et al., 2022 |
| Hypocaloric diet, fasting | Metabolic, autoimmune, and inflammatory diseases | Reduction of systemic inflammation via activation of hepatic AMPK and reduction of systemic CCL2 | Nutrient deficiencies | Gopalarathinam et al., 2024; Gasmi et al., 2018 |
| Prevention of alternating periods of highly processed foods and ‘healthy’ food | Atherosclerosis | Prevention of IL1β-dependent neutrophil reprogramming in the BM | n/a | Lavillegrand et al., 2024 |
| Prevention of weight cycling | Atherosclerosis | Prevention of HSPC reprogramming | n/a | Scolaro et al., 2025 |
| Moderate exercise | Cardiovascular disease | Metabolic rewiring of macrophages: increased OXPHOS and reduced ROS production | n/a | Murugathasan et al., 2023; Zaid et al., 2024 |
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Western lifestyle linked to maladaptive trained immunity
eLife 15:e105835.
https://doi.org/10.7554/eLife.105835
