ArticleProceedings of the National Academy of Sciences of the United States of America2014
Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 151 citations in OpenAlex.
- Pathogenesis of Tuberculosis: Interplay Between Host Antituberculosis Immunity and Immune Evasion Strategies ofMedComm · 2026Review
- miR-9394b from Lactobacillus paracasei extracellular vesicles targets iNOS to reprogram host NO-ornithine metabolism and ameliorate DSS-induced murine colitis.NPJ biofilms and microbiomes · 2026Article
- Photodynamic therapy: A paradigm shift in overcoming drug‑resistant tuberculosis (Review).Molecular medicine reports · 2026Review
- The arginase-polyamine signaling axis in immune cells: Implications for immune modulation and host-pathogen interactions.iScience · 2026Review
- Differential Transcriptomic Features of Peripheral Blood Mononuclear Cells in Pulmonary Sarcoidosis with and Without Extrapulmonary Lesions in an East Asian Population.Biomedicines · 2025Article
- Oral L-Arginine treatment attenuatesVirulence · 2025Article
- Immunopathogenesis of tuberculosis: cellular mechanisms and immune modulation.Veterinary research · 2025Review
- In vivo regulation of the monocyte phenotype by Mycobacterium marinum and the ESX-1 type VII secretion system.Scientific reports · 2025Article
- Inducible antibacterial responses in macrophages.Nature reviews. Immunology · 2025Review
- Arginine metabolism in myeloid cells in health and disease.Seminars in immunopathology · 2025Review
- Microenvironments of tuberculous granuloma: advances and opportunities for therapy.Frontiers in immunology · 2025Review
- Where lung cancer and tuberculosis intersect: recent advances.Frontiers in immunology · 2025Review
- Roles of Critical Amino Acids Metabolism in The Interactions Between Intracellular Bacterial Infection and Macrophage Function.Current microbiology · 2024Review
- Tuberculous pleural effusion-induced Arg-1Respiratory research · 2024Article
- Intestinal Helminth Infections and Their Association with QuantiFERON-TB Gold Plus Test Performance in an Endemic Setting, Northwest Ethiopia.Infection and drug resistance · 2024Article
- From immunology to artificial intelligence: revolutionizing latent tuberculosis infection diagnosis with machine learning.Military Medical Research · 2023Review
- Loss of TRIM24 promotes IL-10 expression via CBP/p300-dependent IFNβ1 transcription during macrophage activation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Regulated Arginine Metabolism in Immunopathogenesis of a Wide Range of Diseases: Is There a Way to Pass between Scylla and Charybdis?Current issues in molecular biology · 2023Review
- Metabolic flux reprogramming inFrontiers in microbiology · 2023Article
- DestVI identifies continuums of cell types in spatial transcriptomics data.Nature biotechnology · 2022Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
Lung granulomas develop upon Mycobacterium tuberculosis (Mtb) infection as a hallmark of human tuberculosis (TB). They are structured aggregates consisting mainly of Mtb-infected and -uninfected macrophages and Mtb-specific T cells. The production of NO by granuloma macrophages expressing nitric oxide synthase-2 (NOS2) via l-arginine and oxygen is a key protective mechanism against mycobacteria. Despite this protection, TB granulomas are often hypoxic, and bacterial killing via NOS2 in these conditions is likely suboptimal. Arginase-1 (Arg1) also metabolizes l-arginine but does not require oxygen as a substrate and has been shown to regulate NOS2 via substrate competition. However, in other infectious diseases in which granulomas occur, such as leishmaniasis and schistosomiasis, Arg1 plays additional roles such as T-cell regulation and tissue repair that are independent of NOS2 suppression. To address whether Arg1 could perform similar functions in hypoxic regions of TB granulomas, we used a TB murine granuloma model in which NOS2 is absent. Abrogation of Arg1 expression in macrophages in this setting resulted in exacerbated lung granuloma pathology and bacterial burden. Arg1 expression in hypoxic granuloma regions correlated with decreased T-cell proliferation, suggesting that Arg1 regulation of T-cell immunity is involved in disease control. Our data argue that Arg1 plays a central role in the control of TB when NOS2 is rendered ineffective by hypoxia.
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Registered trials
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