Summary of project PR002231
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002231. The data can be accessed directly via it's Project DOI: 10.21228/M87R79 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002231 |
| Project DOI: | doi: 10.21228/M87R79 |
| Project Title: | Macrophages recycle phagocytosed bacteria to fuel immunometabolic responses |
| Project Summary: | Macrophages specialize in phagocytosis, a cellular process that eliminates extracellular matter, including microbes, through internalization and degradation. Despite the critical role of phagocytosis during bacterial infection, the fate of phagocytosed microbial cargo and its impact on host cell is poorly understood. Here, we reveal that ingested bacteria constitute an alternative nutrient source that skews immunometabolic host responses. Tracing stable isotope-labelled bacteria, we found that phagolysosomal degradation of bacteria provides carbon atoms and amino acids that are recycled into various metabolic pathways, including glutathione and itaconate biosynthesis, and satisfy macrophage bioenergetic needs. Metabolic recycling of microbially-derived nutrients is regulated by the nutrient sensing mTORC1 and intricately tied to microbial viability. Dead bacteria, as opposed to live ones, are enriched in cyclic- adenosine monophosphate (AMP), sustain the cellular AMP pool and subsequently activate AMP protein kinase (AMPK) to inhibit mTORC1. Consequently, killed bacteria strongly fuel metabolic recycling and support macrophage survival, but elicit decreased reactive oxygen species (ROS) production and a reduced IL-1β secretion compared to viable bacteria. These results reveal a novel insight into the fate of engulfed microbes and highlights a microbial viability-associated metabolite that triggers host metabolic and immune responses. Our findings hold promise for shaping immunometabolic intervention in various immune-related pathologies. |
| Institute: | University of Colorado Anschutz Medical Campus |
| Laboratory: | Lab of Angelo D'Alessandro in collaboration with lab of Johan Garaude (INSERM, Fr) |
| Last Name: | Haines |
| First Name: | Julie |
| Address: | 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA |
| Email: | julie.haines@cuanschutz.edu |
| Phone: | 3037243339 |
Summary of all studies in project PR002231
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003603 | Comparison of metabolic responses in murine bone marrow derived macrophages upon LPS treatment versus following the engulfment of live or dead E coli. | Mus musculus | University of Colorado Anschutz Medical Campus | MS | 2024-12-27 | 1 | 27 | Uploaded data (2G)* |
| ST003604 | Investigation of global metabolites and E coli-derived metabolites following engulfment of dead bacteria by wild type or RagAGTP-expressing bone marrow derived macrophages. | Mus musculus | University of Colorado Anschutz Medical Campus | MS | 2024-12-27 | 1 | 44 | Uploaded data (4.3G)* |
| ST003605 | Global metabolomics and tracing of E coli-derived metabolites following engulfment of heat-killed bacteria by wild type or RagAGTP-deficient bone marrow derived macrophages. | Mus musculus | University of Colorado Anschutz Medical Campus | MS | 2024-12-27 | 1 | 36 | Uploaded data (3.3G)* |
| ST003606 | Global metabolomics and tracing of E coli-derived metabolites following engulfment of live or heat-killed bacteria by bone marrow derived macrophages expressing constitutively active mutants of Kras or Hras | Mus musculus | University of Colorado Anschutz Medical Campus | MS | 2024-12-27 | 1 | 76 | Uploaded data (6.4G)* |
| ST003607 | Global metabolomics and tracing of 13C-labeled metabolites of bone marrow derived macrophages following engulfment of dead 13C-labeled Citrobacter rodentium, Listeria innocua, Staphilococcus aureus, or Pseudomonas aeruginosa. | Mus musculus | University of Colorado Anschutz Medical Campus | MS | 2024-12-27 | 1 | 20 | Uploaded data (2.6G)* |
| ST003608 | Global metabolomics to compare metabolic profiles of live vs heat-killed thymidine-auxotrophe E. Coli | Escherichia coli | University of Colorado Anschutz Medical Campus | MS | 2024-12-27 | 1 | 6 | Uploaded data (704.8M)* |
| ST003609 | 13C-tracing of central energy metabolism in thymidine-auxotroph E. Coli | Escherichia coli | University of Colorado Anschutz Medical Campus | MS | 2024-12-27 | 1 | 6 | Uploaded data (713.6M)* |
| ST003610 | 13C-tracing metabolomics of peritoneal macrophages 1hour and 2hours after engulfment of 13C-labeled heat-killed E coli | Mus musculus | University of Colorado Anschutz Medical Campus | MS | 2024-12-27 | 1 | 19 | Uploaded data (2.3G)* |
| ST003611 | 13C-tracing metabolomics of peritoneal macrophages 1hour after engulfment of 13C-labeled heat-killed E coli vs untreated peritoneal macrophages | Mus musculus | University of Colorado Anschutz Medical Campus | MS | 2024-12-27 | 1 | 10 | Uploaded data (1.3G)* |
