Low protein diet protects the liver from Salmonella Typhimurium-mediated injury by modulating the mTOR/autophagy axis in macrophages
Year: 2024
Type: article
Abstract: 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.
Source: Communications Biology
Authors: Edyta E. Wojtowicz, Katherine Hampton, Mar Moreno-Gonzalez, Charlotte L. Utting, Yuxuan Lan, Paula Ruiz, Gemma Beasy, Caitlin Bone, Charlotte Hellmich, Rebecca Maynard, Luke Acton, Matthew Markham, Linda Troeberg, Andrea Telatin, Robert A. Kingsley, Iain C. Macaulay, Stuart A. Rushworth, Naiara Beraza
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,890
Awards: G1322288588, Supporting EI’s ISPs and the UK Community with Genomics and Single Cell Analysis, Cellular Genomics (CELLGEN): Cell-type specific transcriptional changes during development and upon stress, Investigation of the processes determining mitochondrial fate in normal and malignant haematopoiesis, G1674374521, Changes in gut microbe-host interactions and their impact beyond the gut, G2331260177, G2373856930, Cellular Genomics (CELLGEN): Consequences of somatic genome variation on traits, G2640177428, New Inv. Award: Developing single-cell isoform sequencing tools to explore the diversity and regulation of alternative splicing in haematopoiesis, G3202646069, G3234378675, G3466513604, G3545028318, G3546372931, Norwich Research Park Biosciences Doctoral Training Partnership, G3601653273, G3742038031, G3813641685, G3870339886, G4374402992, BBSRC Institute Strategic Programme: Food Microbiome and Health (FMH) - Partner Grant, G497361211, G5015502491, G5209625341, G5217121905, Cellular Genomics (CELLGEN): Data Science for Cellular Genomics, G5363844604, G5377849018, Enabling and Advancing Life Scientists in data-driven research through Advanced Genomics and Computational Training, G5448826682, G5457109968, Development and deployment of versatile digital platforms for 'omics-based data sharing and analysis, G5945011414, G6225108827, G6310548300, G6362852793, G6409707310, Investigating the ageing phenotype in the bone marrow microenvironment: the role of macrophages in regulating normal and malignant haematopoiesis, G7075711930, G7251429314, G7305703845, G7318838661, BBSRC National Bioscience Research Infrastructure: Transformative Genomics, G7669914618, G7835025966, Role of LAP in controlling liver homeostasis, G8472532665, G8613541369, Unravelling key regulators of thrombopoiesis using a novel RNA based clonal and molecular approaches, G917981861, G926259237, G937519574
OpenAlex ID: W4403001915