Monocytes re-enter the bone marrow during fasting and alter the host response to infection

Diet profoundly influences physiology. Whereas over-nutrition elevates risk for disease via its influence on immunity and metabolism, caloric restriction and fasting appear to be salutogenic. Despite multiple correla-tions observed between diet and health, the underlying biology remains unclear. Here, we identified a fasting -induced switch in leukocyte migration that prolongs monocyte lifespan and alters susceptibility to disease in mice. We show that fasting during the active phase induced the rapid return of monocytes from the blood to the bone marrow. Monocyte re-entry was orchestrated by hypothalamic-pituitary-adrenal (HPA) axis -depen-dent release of corticosterone, which augmented the CXCR4 chemokine receptor. Although the marrow is a safe haven for monocytes during nutrient scarcity, re-feeding prompted mobilization culminating in monocy-tosis of chronologically older and transcriptionally distinct monocytes. These shifts altered response to infec-tion. Our study shows that diet-in particular, a diet's temporal dynamic balance-modulates monocyte lifespan with consequences for adaptation to external stressors.

Automated summary

Diet plays a profound role in physiological processes, with over-nutrition increasing disease risk while caloric restriction and fasting have beneficial effects. However, the underlying biology connecting diet and health is still unclear. In this study, fasting was found to induce a switch in leukocyte migration, prolonging monocyte lifespan and altering susceptibility to disease in mice. This effect was mediated by the release of corticosterone through the hypothalamic-pituitary-adrenal (HPA) axis, which enhanced the CXCR4 chemokine receptor. These findings highlight the importance of diet, particularly its temporal dynamics, in modulating monocyte lifespan and response to external stressors.