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Wojtowicz, Edyta E., Hampton, Katherine, Moreno-Gonzalez, Mar, Utting, Charlotte L., Lan, Yuxuan, Ruiz, Paula, Beasy, Gemma, Bone, Caitlin, Hellmich, Charlotte, Maynard, Rebecca, Acton, Luke, Markham, Matthew, Troeberg, Linda 
ORCID: https://orcid.org/0000-0003-0939-4651, Telatin, Andrea, Kingsley, Robert A. ORCID: https://orcid.org/0000-0002-0194-6485, Macaulay, Iain C., Rushworth, Stuart A. and Beraza, Naiara
(2024)
Low protein diet protects the liver from Salmonella Typhimurium-mediated injury by modulating the mTOR/autophagy axis in macrophages.
Communications Biology, 7.
ISSN 2399-3642
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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.
| Item Type: | Article |
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| Additional Information: | Data availability statement: Bulk RNA-seq and scRNA-seq data generated for this study have been deposited at ENA and are publicly accessible using accession number:PRJEB74911. The underlying raw data shown in Figs. 1–5 can be found in Supplemental Data 1. Additional Supplementary results are shown in Supplemental material and corresponding raw data can be found in Supplemental Data 2. The authors declare that all data generated from this study are available within the manuscript and the supplemental material provided. Any additional files or information can be provided upon request to the corresponding authors. Funding information: The authors gratefully acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Programme Gut Microbes and Health BB/R012490/1 and its constituent project BBS/E/F/000PR10355, and the BBSRC Core Capability Grant BB/CCG1860/1 as well as the BBSRC Institute Strategic Programme Food Microbiomes and Health BB/X011054/1 and its constituent project BBS/E/F/000PR13632 (N.B.) and Microbes and Food Safety (BB/X011011/1) And its constituent BBS/E/F/000PR13634. K.H. was supported by the UKRI BBSRC Norwich research park Bioscience doctoral training programme BB/T008717/1. P.R. is supported by a BBSRC response mode BB/W002450/1 (to N.B.). S.A.R. was supported by the UKRI MRC project (MR/T02934X/1) and BBSRC BB/X01889X/1 (QIB/UEA partnership). C.H. was supported by the Wellcome Trust Clinical Research Fellowship (220534/Z/20/Z). E.W. and I.C.M. acknowledge support from the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation, Core Capability Grant BB/CCG1720/1 and the National Capability BBS/E/T/000PR9816, BBS/E/T/000PR9814, BBS/E/T/000PR9811. E.W. and I.C.M. acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation; Earlham Institute Strategic Programme Grant Cellular Genomics BBX011070/1 and its constituent work packages(s): BBS/E/ER/230001B and BBS/E/ER/230001C. Part of this work was delivered via Transformative Genomics the BBSRC funded National Bioscience Research Infrastructure (BBS/E/ER/23NB0006) at Earlham Institute by members of the Single-Cell and Spatial Analysis Group, Genomics Pipelines and Core Bioinformatics Groups. EW was supported by the Sir Henry Wellcome Postdoctoral fellowship (213731/Z/18/Z). ICM was additionally supported by BBSRC New Investigator Grant BB/P022073/1.The author(s) acknowledge support from the BBSRC, part of UK Research and Innovation, Core Capability Grant BB/CCG1720/1 and the National Capability (BBS/E/T/000PR9816). |
| Uncontrolled Keywords: | medicine (miscellaneous),biochemistry, genetics and molecular biology(all),agricultural and biological sciences(all),sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2701 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging |
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| Depositing User: | LivePure Connector |
| Date Deposited: | 23 Oct 2024 09:30 |
| Last Modified: | 28 Oct 2024 00:53 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97128 |
| DOI: | 10.1038/s42003-024-06932-w |
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