Highlights

•Circulating monocytes migrate to the bone marrow upon fasting
•Monocytes augment CXCR4 via a fasting-induced hormonal stress response
•Re-feeding after prolonged fasting results in a surge of monocytes into circulation
•Prolonged fasting and re-feeding alter the immune response to bacterial infection

Summary
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 correlations 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-dependent 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 monocytosis of chronologically older and transcriptionally distinct monocytes. These shifts altered response to infection.

Our study shows that diet—in particular, a diet’s temporal dynamic balance—modulates monocyte lifespan with consequences for adaptation to external stressors

https://www.cell.com/immunity/fulltext/S1074-7613(23)00036-5