Earlham Institute, Cellular Genomics Strategic Programme, Norwich Research Park, Norwich, UK, Norwich Research Park, Norwich, UK.
Metabolic Health Research Centre, Faculty of Medicine, University of East Anglia, Norwich Research Park, Norwich, UK.
Commun Biol. 2024 Sep 30;7(1):1219. doi: 10.1038/s42003-024-06932-w.
Western diets are the underlying cause of metabolic and liver diseases. Recent trend to limit the consumption of protein-rich animal products has become more prominent. This dietary change entails decreased protein consumption; however, it is still unknown how this affects innate immunity. Here, we studied the influence of a low protein diet (LPD) on the liver response to bacterial infection in mice. We found that LPD protects from Salmonella enterica serovar Typhimurium (S. Typhimurium)-induced liver damage. Bulk and single-cell RNA sequencing of murine liver cells showed reduced inflammation and upregulation of autophagy-related genes in myeloid cells in mice fed with LPD after S. Typhimurium infection. Mechanistically, we found reduced activation of the mammalian target of rapamycin (mTOR) pathway, whilst increased phagocytosis and activation of autophagy in LPD-programmed macrophages. We confirmed these observations in phagocytosis and mTOR activation in metabolically programmed human peripheral blood monocyte-derived macrophages. Together, our results support the causal role of dietary components on the fitness of the immune system.
西方饮食是代谢和肝脏疾病的根本原因。最近限制富含蛋白质的动物产品消费的趋势变得更加明显。这种饮食变化意味着蛋白质的摄入量减少；然而，目前尚不清楚这如何影响先天免疫。在这里，我们研究了低蛋白饮食（LPD）对小鼠细菌感染后肝脏反应的影响。我们发现，LPD 可预防沙门氏菌肠炎亚种（S. Typhimurium）引起的肝损伤。对感染 S. Typhimurium 后接受 LPD 喂养的小鼠的肝脏细胞进行的 bulk 和单细胞 RNA 测序显示，髓样细胞中的炎症减少和自噬相关基因的上调。从机制上讲，我们发现 LPD 程序性巨噬细胞中哺乳动物雷帕霉素靶蛋白（mTOR）途径的激活减少，而吞噬作用和自噬的激活增加。我们在代谢编程的人外周血单核细胞衍生的巨噬细胞中的吞噬作用和 mTOR 激活中证实了这些观察结果。总之，我们的研究结果支持饮食成分对免疫系统适应性的因果作用。
