ArticleNature microbiology2025
Metabolic remodelling produces fumarate via the aspartate-argininosuccinate shunt in macrophages as an antiviral defence.
Article in Nature microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Probiotic extracellular vesicles reprogram macrophage immunometabolism: From gut crosstalk to host health.Gut microbes · 2026Review
- Inducible chronic NAD deficiency in mice reveals multi-systemic phenotypical, metabolic, and transcriptional changes.Nature communications · 2026Article
- Endogenous metabolite signaling orchestrates tumor immune evasion.Cell insight · 2026Review
- Metabolites as signalling molecules in the tumour immune microenvironment.Nature reviews. Immunology · 2026Review
- Engineered Bacterial Nanosyringes Induce Transient and Controllable Hepatic Immune-Metabolic Responses.Journal of microbiology and biotechnology · 2026Article
- Viral-host interactions mediated by the mTOR signaling pathway.Cell insight · 2026Review
- Integrative proteomic and metabolomic analysis reveals that ouabain inhibits DLBCL proliferation by reprogramming arginine-driven metabolic networks.Frontiers in pharmacology · 2026Article
- White spot syndrome virus IE1 protein hijacks the host pentose phosphate pathway to fuel viral replication.PLoS pathogens · 2026Article
- The immunometabolic axis of sepsis-related myocardial injury: macrophage reprogramming as a central mechanism and therapeutic target.Frontiers in immunology · 2026Review
- Neoepitopes at the crossroads of immunometabolism: metabolic remodeling of antigen presentation in type 1 diabetes.Frontiers in immunology · 2026Review
- Temporal dynamics of macrophage activation duringVirulence · 2025Article
- Article
- An inherited mitochondrial DNA mutation remodels inflammatory cytokine responses in macrophages and in vivo in mice.Nature communications · 2025Article
- The RIG-I-like receptor family of immune proteins.Molecular cell · 2025Review
- Mitochondria reactive oxygen species signaling-dependent immune responses in macrophages and T cells.Immunity · 2025Review
- Lysophosphatidylcholine as a Novel Diagnostic Biomarker in Kawasaki Disease: Based on Immunometabolism-Related Signature.Journal of inflammation research · 2025Article
- Macrophage polarization: molecular mechanisms, disease implications, and targeted therapeutic strategies.Frontiers in immunology · 2025Review
Corrections and comments
- Erratum issued
- Expression of concern
- Retracted
Authors and funding
5 authors.
Funding
Abstract
Metabolic remodelling underpins macrophage effector functions in response to various stimuli, but the mechanisms involved are unclear. Here we report that viral-infection-induced inflammatory stimulation causes a rewiring of the urea cycle and the tricarboxylic acid cycle metabolism in macrophages to form a cyclic pathway called the aspartate-argininosuccinate (AAS) shunt. Using RNA sequencing, unbiased metabolomics and stable isotope tracing, we found that fumarate generated from the AAS shunt is driven by argininosuccinate synthase (ASS1) in the cytosol and potentiates inflammatory effects. Genetic ablation of ASS1 reduces intracellular fumarate levels and interferon-β production, and mitochondrial respiration is also suppressed. Notably, viral challenge or fumarate esters enhance interferon-β production via direct succination of the mitochondrial antiviral signalling protein and activation of the retinoic acid-inducible gene-I-like receptor signalling. In addition to the vesicular stomatitis virus, the Sendai virus and influenza A virus can also exert these effects. In addition, patients with Ebola virus disease have increased ASS1 expression and ASS1-deficient mice show suppressed macrophage interferon responses to vesicular stomatitis virus infection. These findings reveal that fumarate can be produced from the viral inflammation-induced AAS shunt and is essential for antiviral innate immunity.
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