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

Janssen, Henrike; Kahles, Florian; Liú, Dan; Downey, Jeffrey; Koekkoek, Laura L.; Roudko, Vladimir; D’souza, Darwin; McAlpine, Cameron S.; Halle, Lennard; Poller, Wolfram C.; Chan, Christopher T.; He, Shasha; Mindur, John E.; Kiss, Máté G.; Singh, Sumnima; Anzai, Atsushi; Iwamoto, Yoshiko; Köhler, Rainer H.; Chetal, Kashish; Sadreyev, Ruslan I.; Weissleder, Ralph; Kim‐Schulze, Seunghee; Mérad, Miriam; Nahrendorf, Matthias; Świrski, Filip K.

doi:10.1016/j.immuni.2023.01.024

Cited by 63 publications

(33 citation statements)

References 55 publications

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“…The response of immune cell populations to DR is complex yet clearly important as an indicator of efficacy of DR. Our findings reveal that DR exacerbates the age-related decline in mature CD11b + NK cells and reduces the level of circulating inflammatory monocytes in a calorie titratable manner, while the increase in percent of circulating B cells with age was completely inhibited only by 40% CR. A recent study indicated that DR modifies trafficking of immune cells between the circulation and tissue sites 66 . Thus, the observed changes in immune cell subsets impacted by diet may have been reflective of differences in tissue residence induced by acute effects of fasting and timing of blood sampling.…”

Section: Supplementary Discussionmentioning

confidence: 99%

Regulators of health and lifespan extension in genetically diverse mice on dietary restriction

Di Francesco,

Deighan,

Litichevskiy

et al. 2023

Preprint

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SummaryCaloric restriction (CR) delays aging and extends healthy lifespan in multiple species. Alternative forms of dietary restriction (DR) such as intermittent fasting (IF) have drawn significant interest as a more sustainable regimen, but the landscape of longevity-promoting dietary interventions remains largely unexplored. Identifying the most robust, efficacious, and experimentally tractable modes of DR is key to better understanding and implementing effective longevity interventions for human healthspan. To that end, we have performed an extensive assessment of DR interventions, investigating the effects of graded levels of CR (20% and 40%) and IF (1 day and 2 days of fasting per week) on the health and survival of 960 genetically diverse female mice. All interventions extended lifespan, although only CR significantly reduced the mortality doubling time. Notably, IF did not extend lifespan in mice with high pre-intervention bodyweight. We carried out extensive phenotyping to determine the health effects of long-term DR and to better understand the mechanisms driving within-diet heterogeneity in lifespan. The top within-diet predictor of lifespan was the ability of mice to maintain bodyweight through periods of handling, an indicator of stress resilience. Additional predictors of long lifespan include specific changes in immune cells, red blood cell distribution width (RDW), and retention of adiposity in late life. We found that lifespan is heritable (h2= 0.24), and that genetic background has a larger influence on lifespan than dietary interventions. We identified a significant association for lifespan and RDW on chromosome 18 that explained 4.3% of the diet-adjusted variation in lifespan. Diet-induced changes on metabolic traits, although beneficial, were relatively poor predictors of lifespan, arguing against the long-standing notion that DR works by counteracting the negative effects of obesity. These findings indicate that improving health and extending lifespan are not synonymous and that metabolic parameters may be inappropriate endpoints for evaluating aging interventions in preclinical models and clinical trials.

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Section: Supplementary Discussionmentioning

confidence: 99%

Regulators of health and lifespan extension in genetically diverse mice on dietary restriction

Di Francesco,

Deighan,

Litichevskiy

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Numerous studies have described the effects of fasting and caloric restriction on redistribution of memory T cells, monocytes, and B cells to the BM, and facilitation of CD8 + T-cell tumor control. [9][10][11]76,77 Additionally, fasting and fasting-mimicking diets show profound effects on tumor cells by promoting an anti-Warburg effect and inducing sensitivity to chemotherapy. [78][79][80] Clinical trials implementing these diets are yielding promising results, including enhanced tumor responsiveness to therapies, where improved immune responses were observed.…”

Section: Cell-intrinsic Responsesmentioning

confidence: 99%

“…In the immune system, dietary changes impact immune composition and responses both systemically and within tissues. Numerous studies have described the effects of fasting and caloric restriction on redistribution of memory T cells, monocytes, and B cells to the BM, and facilitation of CD8 + T‐cell tumor control 9–11,76,77 . Additionally, fasting and fasting‐mimicking diets show profound effects on tumor cells by promoting an anti‐Warburg effect and inducing sensitivity to chemotherapy 78–80 .…”

Section: Diet Shapes Immunometabolism and Immune Cell Functionmentioning

confidence: 99%

Metabolic programming of organ‐specific natural killer cell responses

Delconte,

Sun

2024

Immunological Reviews

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SummaryCells of the mammalian innate immune system have evolved to protect the host from various environmental or internal insults and injuries which perturb the homeostatic state of the organism. Among the lymphocytes of the innate immune system are natural killer (NK) cells, which circulate and survey host tissues for signs of stress, including infection or transformation. NK cells rapidly eliminate damaged cells in the blood or within tissues through secretion of cytolytic machinery and production of proinflammatory cytokines. To perform these effector functions while traversing between the blood and tissues, patrolling NK cells require sufficient fuel to meet their energetic demands. Here, we highlight the ability of NK cells to metabolically adapt across tissues, during times of nutrient deprivation and within tumor microenvironments. Whether at steady state, or during viral infection and cancer, NK cells readily shift their nutrient uptake and usage in order to maintain metabolism, survival, and function.

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“…[ 43 ] Additionally, the latest study found that fasting induces rapid return of mice monocytes from the blood to the bone marrow through the release of hypothalamic pituitary adrenal (HPA) axis dependent corticosterone. [ 44 ] Given that TAMs are derived from circulating monocytic precursors, these studies suggest that CR/fasting may also decrease TAM infiltration into tumors by reducing CCL2 levels. However, it should be also noted that the macrophage responses during CR/fasting are likely to vary between different tissues and disease conditions due to the complexity of macrophage polarization and metabolism.…”

Section: Effects Of Fasting On Macrophage Subsetsmentioning

confidence: 99%

Effects of Calorie Restriction and Fasting on Macrophage: Potential Impact on Disease Outcomes?

Wang,

et al. 2023

Molecular Nutrition Food Res

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Energy restriction, including calorie restriction and fasting, has garnered significant attention for its potential therapeutic effects on a range of chronic diseases (such as diabetes, obesity, and cancer) and aging. Since macrophages are critical players in many diseases, their response to energy restriction may impact disease outcomes. However, the diverse metabolic patterns and functions of macrophages can lead to variability in the effects of energy restriction on macrophages across different tissues and disease states. This review outlines the effects of energy restriction on macrophages in several diseases, offering valuable guidance for future studies and insights into the clinical applications of calorie restriction and fasting.

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

Cited by 63 publications

References 55 publications

Regulators of health and lifespan extension in genetically diverse mice on dietary restriction

Regulators of health and lifespan extension in genetically diverse mice on dietary restriction

Metabolic programming of organ‐specific natural killer cell responses

Effects of Calorie Restriction and Fasting on Macrophage: Potential Impact on Disease Outcomes?

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