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Integrated metabolic-transcriptomic network identifies immunometabolic modulations in human macrophages
Hung-Jen Chen1, Daniel C Sévin2, Guillermo R Griffith1
1Department of Medical Biochemistry, Experimental Vascular Biology, Atherosclerosis and Ischemic Syndromes, Amsterdam Cardiovascular Sciences, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam University Medical Center, Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
Cell Reports
|September 14, 2024
Summary
This study reveals how macrophage metabolism impacts immune responses. Inhibiting tryptophan metabolism and understanding cholesterol
Area of Science:
- Immunology
- Metabolomics
- Systems Biology
Background:
- Macrophages display diverse phenotypes and adapt their metabolism.
- Metabolic reprogramming is crucial for macrophage functional plasticity.
Purpose of the Study:
- To investigate the metabolic impact on human macrophage function using a multi-omics dataset.
- To establish a metabolite-gene correlation network for characterizing macrophage activation.
Main Methods:
- Integration of intra- and extracellular metabolomes with transcriptomic data.
- Construction of a metabolite-gene correlation network.
- Analysis of macrophage responses to specific metabolic modulations.
Main Results:
- Concurrent inhibition of tryptophan catabolism (IDO1, IL4I1) suppresses pro-inflammatory responses.
- Single inhibition of these enzymes leads to pro-inflammatory activation.
- Anti-inflammatory macrophages can promote glycolysis, contrary to prior assumptions.
- Cholesterol accumulation inhibits macrophage interferon-gamma (IFN-γ) responses.
Conclusions:
- The integrated network provides insights into macrophage immunometabolic reprogramming.
- Identified immunometabolic features offer potential therapeutic targets for immune disorders.
- This resource aids researchers studying macrophage immunometabolism.
