ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Differential Requirements for L-Citrulline and L-Arginine during Antimycobacterial Macrophage Activity.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Impact of L-arginine and L-citrulline supplementation on macrophage responses toFrontiers in immunology · 2026Article
- Exogenous arginine differentially regulates inflammatory cytokine and inducible nitric oxide synthase expression in macrophages.ImmunoHorizons · 2025Article
- Arginine metabolism in myeloid cells in health and disease.Seminars in immunopathology · 2025Review
- Host M-CSF induced gene expression drives changes in susceptible and resistant mice-derived BMdMs uponFrontiers in immunology · 2023Article
- The Role of Amino Acids in Tuberculosis Infection: A Literature Review.Metabolites · 2022Review
- Targeted metabolomics analysis of serum and Mycobacterium tuberculosis antigen-stimulated blood cultures of pediatric patients with active and latent tuberculosis.Scientific reports · 2022Article
- Cutting Edge: l-Arginine Transfer from Antigen-Presenting Cells Sustains CD4Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Modulating macrophage function to reinforce host innate resistance againstFrontiers in immunology · 2022Review
- Itaconate, Arginine, and Gamma-Aminobutyric Acid: A Host Metabolite Triad Protective Against Mycobacterial Infection.Frontiers in immunology · 2022Review
- Review
- UPLC-ESI-Q-TOF-MS-Based Metabolite Profiling, Antioxidant and Anti-Inflammatory Properties of Different Organ Extracts ofAntioxidants (Basel, Switzerland) · 2021Article
- Host Immune-Metabolic Adaptations Upon Mycobacterial Infections and Associated Co-Morbidities.Frontiers in immunology · 2021Review
- Promotion of Anti-Tuberculosis Macrophage Activity by L-Arginine in the Absence of Nitric Oxide.Frontiers in immunology · 2021Article
- Imatinib modulates pro-inflammatory microenvironment with angiostatic effects in experimental lung carcinogenesis.Inflammopharmacology · 2020Article
- Short-Term Supplementation of Dietary Arginine and Citrulline Modulates Gilthead Seabream (Frontiers in immunology · 2020Article
- Cell type-specific mechanisms coupling protease-activated receptor-1 to infectious colitis pathogenesis.Journal of thrombosis and haemostasis : JTH · 2020Article
- Susceptibility to Intracellular Infections: Contributions of TNF to Immune Defense.Frontiers in microbiology · 2020Review
- An Army Marches on Its Stomach: Metabolic Intermediates as Antimicrobial Mediators inFrontiers in cellular and infection microbiology · 2020Review
- Metabolic Regulation of Immune Responses toFrontiers in immunology · 2020Review
- Plasma metabolomics in tuberculosis patients with and without concurrent type 2 diabetes at diagnosis and during antibiotic treatment.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Microbicidal NO production is reliant on inducible NO synthase-mediated L-arginine metabolism in macrophages (MΦs). However, L-arginine supply can be restricted by arginase activity, resulting in inefficient NO output and inhibition of antimicrobial MΦ function. MΦs circumvent this by converting L-citrulline to L-arginine, thereby resupplying substrate for NO production. In this article, we define the metabolic signature of mycobacteria-infected murine MΦs supplied L-arginine, L-citrulline, or both amino acids. Using liquid chromatography-tandem mass spectrometry, we determined that L-arginine synthesized from L-citrulline was less effective as a substrate for arginase-mediated L-ornithine production compared with L-arginine directly imported from the extracellular milieu. Following Mycobacterium bovis bacillus Calmette-Guérin infection and costimulation with IFN-γ, we observed that MΦ arginase activity did not inhibit production of NO derived from L-citrulline, contrary to NO inhibition witnessed when MΦs were cultured in L-arginine. Furthermore, we found that arginase-expressing MΦs preferred L-citrulline over L-arginine for the promotion of antimycobacterial activity. We expect that defining the consequences of L-citrulline metabolism in MΦs will provide novel approaches for enhancing immunity, especially in the context of mycobacterial disease.
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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.