Low protein diet protects the liver from Salmonella Typhimurium-mediated injury by modulating the mTOR/autophagy axis in macrophages
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.
Authors
- Luke Acton (ORCID: https://orcid.org/0000-0001-9116-7866)
- Rebecca S Maynard (ORCID: https://orcid.org/0009-0001-1231-6569)
- Caitlin Bone (ORCID: https://orcid.org/0000-0002-5881-3202)
- Katherine Hampton (ORCID: https://orcid.org/0000-0002-7563-0213)
- Andrea Telatin (ORCID: https://orcid.org/0000-0001-7619-281X)
- Yuxuan Lan (ORCID: https://orcid.org/0000-0002-1652-4250)
- Robert A. Kingsley (ORCID: https://orcid.org/0000-0002-0194-6485)
- Charlotte Hellmich (ORCID: https://orcid.org/0000-0002-5395-9982)
- Iain C. Macaulay (ORCID: https://orcid.org/0000-0002-6761-757X)
- Paula Ruiz
- Gemma Beasy
- Naiara Beraza (ORCID: https://orcid.org/0000-0003-0718-0940)
- Charlotte Utting (ORCID: https://orcid.org/0009-0005-7998-9214)
- Mar Moreno‐Gonzalez (ORCID: https://orcid.org/0000-0002-5840-5751)
- Edyta E. Wojtowicz (ORCID: https://orcid.org/0000-0003-0531-2807)
- Stuart A. Rushworth (ORCID: https://orcid.org/0000-0002-3711-7558)
- Linda Troeberg
- Matthew Markham
Institutions
- University of East Anglia (GB)
- Norwich Research Park (GB)
- Norfolk and Norwich University Hospital (GB)
- Quadram Institute (GB)
Publication Details
- Journal
- Communications Biology
- Published
- 2024-09-30
- DOI
- https://doi.org/10.1038/s42003-024-06932-w
- Citations
- 6
- Primary Topic
- Phagocytosis and Immune Regulation
- Type
- article
- Field-Weighted Citation Impact
- 1.44
Funders
- Wellcome Trust
- UK Research and Innovation
- Directorate for Biological Sciences
- Medical Research Council
- Biotechnology and Biological Sciences Research Council