ArticleCell host & microbe2012
Sustained generation of nitric oxide and control of mycobacterial infection requires argininosuccinate synthase 1.
Article in Cell host & microbe, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
103 citing papers in PubMed, 176 citations in OpenAlex.
- Dynamic metabolic programming of monocyte-derived cells defines immunity in CNS disease.Brain : a journal of neurology · 2026Review
- Pathogenesis of Tuberculosis: Interplay Between Host Antituberculosis Immunity and Immune Evasion Strategies ofMedComm · 2026Review
- Self-Generated NO/ROS Nanoreactor Drives Bacterial Clearance and Angiogenesis in Diabetic Wounds.Chem & bio engineering · 2026Article
- ACOD1 regulates microglial arginine metabolism and inflammatory responses.Frontiers in immunology · 2026Article
- A serum metabolite-based machine learning model predicts response to neoadjuvant immunotherapy in mismatch repair-deficient colorectal cancer.Frontiers in oncology · 2026Article
- Combination of single-cell and bulk RNA-seq reveals changes in the immune landscape in osteomyelitis.Frontiers in immunology · 2026Article
- Dermal fibroblast cultures recapitulate differences between deermice and mice in responses to a Toll-like receptor agonist.bioRxiv : the preprint server for biology · 2025Article
- MCT1-mediated Lactate Shuttle to Mitochondria Governs Macrophage Polarization and Modulates Glucose Homeostasis by Affecting β Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exogenous arginine differentially regulates inflammatory cytokine and inducible nitric oxide synthase expression in macrophages.ImmunoHorizons · 2025Article
- Antigen-specific CD4+ T cells promote monocyte recruitment and differentiation into glycolytic lung macrophages to control Mycobacterium tuberculosis.PLoS pathogens · 2025Article
- Dissecting inflammation in the immunemetabolomic era.Cellular and molecular life sciences : CMLS · 2025Review
- The roles of arginases and arginine in immunity.Nature reviews. Immunology · 2025Review
- Citrulline regulates macrophage metabolism and inflammation to counter aging in mice.Science advances · 2025Article
- Macrophages in graft-versus-host disease (GVHD): dual roles as therapeutic tools and targets.Clinical and experimental medicine · 2025Review
- Arginine metabolism in myeloid cells in health and disease.Seminars in immunopathology · 2025Review
- IFN-γ-Driven macrophage responses in the immunity toFrontiers in cellular and infection microbiology · 2025Review
- Dermal fibroblast cultures recapitulate differences between deermice and mice in their responses to a Toll-like receptor agonist.Frontiers in immunology · 2025Article
- Roles of Critical Amino Acids Metabolism in The Interactions Between Intracellular Bacterial Infection and Macrophage Function.Current microbiology · 2024Review
- Emerging nanomaterials targeting macrophage adapted to abnormal metabolism in cancer and atherosclerosis therapy (Review).International journal of molecular medicine · 2024Review
- Glutamine metabolism inhibition has dual immunomodulatory and antibacterial activities against Mycobacterium tuberculosis.Nature communications · 2023Article
43 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Nitric oxide (NO) defends against intracellular pathogens, but its synthesis must be regulated due to cell and tissue toxicity. During infection, macrophages import extracellular arginine to synthesize NO, generating the byproduct citrulline. Accumulated intracellular citrulline is thought to fuel arginine synthesis catalyzed by argininosuccinate synthase (Ass1) and argininosuccinate lyase (Asl), which would lead to abundant NO production. Instead, we find that citrulline is exported from macrophages during early stages of NO production with <2% retained for recycling via the Ass1-Asl pathway. Later, extracellular arginine is depleted, and Ass1 expression allows macrophages to synthesize arginine from imported citrulline to sustain NO output. Ass1-deficient macrophages fail to salvage citrulline in arginine-scarce conditions, leading to their inability to control mycobacteria infection. Thus, extracellular arginine fuels rapid NO production in activated macrophages, and citrulline recycling via Ass1 and Asl is a fail-safe system that sustains optimum NO production.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.