Low protein diet protects the liver from Salmonella Typhimurium-mediated injury by modulating the mTOR/autophagy axis in macrophages.

Wojtowicz EE., Hampton K., Moreno-Gonzalez M., Utting CL., Lan Y., Ruiz P., Beasy G., Bone C., Hellmich C., Maynard R., Acton L., Markham M., Troeberg L., Telatin A., Kingsley RA., Macaulay IC., Rushworth SA., Beraza N.

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.

DOI

10.1038/s42003-024-06932-w

Type

Journal article

Publication Date

2024-09-01T00:00:00+00:00

Volume

7

Addresses

Earlham Institute, Cellular Genomics Strategic Programme, Norwich Research Park, Norwich, UK, Norwich Research Park, Norwich, UK.

Keywords

Liver, Macrophages, Animals, Mice, Inbred C57BL, Humans, Mice, Salmonella typhimurium, Salmonella Infections, Diet, Protein-Restricted, Signal Transduction, Phagocytosis, Autophagy, Male, TOR Serine-Threonine Kinases

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