Dietary intake regulates the circulating inflammatory monocyte pool

Abstract

Caloric restriction is known to improve inflammatory and autoimmune diseases. However, the mechanisms by which reduced caloric intake modulates inflammation are poorly understood. Here we show that short-term fasting reduced monocyte metabolic and inflammatory activity and drastically reduced the number of circulating monocytes. 5Regulation of peripheral monocyte numbers was dependent on dietary glucose and protein levels. Specifically, we found that activation of the low-energy sensor 5'-AMP-activated protein kinase (AMPK) in hepatocytes and suppression of systemic CCL2 production by peroxisome proliferator-activator receptor alpha (PPARα) reduced monocyte mobilization from the bone marrow. Importantly, while caloric restriction improves chronic inflammatory 10 diseases, fasting did not compromise monocyte emergency mobilization during acute infectious inflammation and tissue repair. These results reveal that caloric intake and liver energy sensors dictate the blood and tissue immune tone and link dietary habits to inflammatory disease outcome. 15

Differential regulation of the immune system in a brain-liver-fats organ network during short term fasting

“…While our study was not purposed to decipher the molecular communication between organs or to investigate the migratory behaviors or composition of immune cells under fasting conditions [4][5][6], our study highlights the centrality of immune-transcriptomic modulations during STF. Using a combinatorial data analysis approach, we provide evidence for the existence of an organ network, formed by the similarities of their biological processes, and the prominent role of the immune system in sensing and modulating systemic homeostatic perturbations in the absence of infection.…”

“…In sum, our study provides evidence of a consortium of organ adaptation to short-term energy deprivation, in which the immune system plays a central role. Furthermore, we added insights to the molecular events of fasting-induced priming of T cell-mediated immunity, underlining a putative multi-organ effort to support, at the transcriptome level, the recently reported egress of T and B cells to the bone marrow during periods of systemic energy reduction [5,6].…”

“…However, the mechanisms underlying fasting-induced effects on the immune system remain largely unknown and only recently started to be elucidated [83]. Three recent studies demonstrated that monocytes, naïve B cells, and memory CD8 T cells use bone marrow as a refuge during periods of energy reduction to maintain systemic immune-responsiveness [4][5][6]. These studies also provided new insights into the integrated immunometabolic response in a state of energy deprivation.…”

“…These various forms of reduction in food consumption have many beneficial effects on health, including weight reduction, amelioration of autoimmune diseases, and increased lifespan [2,3]. In line with this, a triad of recent studies demonstrated the ability of different forms of fasting on changing the level and functions of the various immune cell types [4][5][6]. Recently, the interest and applicability of fasting to treat various conditions are as such that they have generated momentum in clinical trials [7][8][9].…”

Metabolic determinants of lupus pathogenesis

“…Within the innate immune system, circulating monocyte frequency and functionality were reduced in response to fasting in both humans and mice, which improved clinical parameters in EAE. 74 Similarly, intermittent fasting was protective in EAE, 75,76 and protection was mediated at least in part by microbiota changes. 76 Protective microbiota changes have also been observed in response to CR in a model of induced colitis and in human inflammatory bowel disease, 14 suggesting that it may be a major mechanism for the immunomodulatory effect of CR.…”