ArticleInfection and immunity2013
The intracellular environment of human macrophages that produce nitric oxide promotes growth of mycobacteria.
Article in Infection and immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Immune dysregulation in tuberculosis-diabetes comorbidity: mechanistic and translational insights.Frontiers in immunology · 2026Pooled it
- Epigenetic silencing of the human NOS2 gene: rethinking the role of nitric oxide in human macrophage inflammatory responses.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Plasma protein signatures altered before and after tuberculosis diagnosis in a population-based cohort.Clinical proteomics · 2026Article
- IFNγ blockade in Mycobacterium tuberculosis infected macaques alters the granuloma environment but not bacterial control.Nature communications · 2026Article
- Hijacking anaerobic metabolism to restore antibiotic efficacy inApplied and environmental microbiology · 2025Article
- Nitric Oxide Contributes to the Pathogenesis ofMicroorganisms · 2025Article
- The microbiome and gut-lung axis in nontuberculous mycobacterial pulmonary disease.PLoS pathogens · 2025Review
- Interferon-γ Stimulation Fails to Restrict Mycobacterium tuberculosis Growth in Human Monocyte-Derived and Alveolar Macrophages.The Journal of infectious diseases · 2025Article
- Arginine metabolism in myeloid cells in health and disease.Seminars in immunopathology · 2025Review
- Intestinal microbiome dysbiosis increaseseLife · 2024Article
- Intracellular peroxynitrite perturbs redox balance, bioenergetics, and Fe-S cluster homeostasis in Mycobacterium tuberculosis.Redox biology · 2024Review
- Exploring host-pathogen interactions in the Dictyostelium discoideum-Mycobacterium marinum infection model of tuberculosis.Disease models & mechanisms · 2024Review
- Nitric oxide brings innate immune resistance toJournal of biosciences · 2024Article
- Nitric oxide is a host cue for Salmonella Typhimurium systemic infection in mice.Communications biology · 2023Article
- The Problem of Host and Pathogen Genetic Variability for Developing Strategies of Universally Efficacious Vaccination against and Personalised Immunotherapy of Tuberculosis: Potential Solutions?International journal of molecular sciences · 2023Article
- Interleukin-27 impairs BCG antigen clearance and T cell stimulatory potential by neonatal dendritic cells.Current research in microbial sciences · 2023Article
- Delineating transcriptional crosstalk between Mycobacterium avium subsp. paratuberculosis and human THP-1 cells at the early stage of infection via dual RNA-seq analysis.Veterinary research · 2022Article
- Sphingosine-1-phosphate receptors 2 and 3 reprogram resting human macrophages into M1 phenotype following mycobacteria infection.Current research in immunology · 2022Article
- Molecular mechanism of interaction ofBiochemistry and biophysics reports · 2021Article
- The interplay between airway epithelium and the immune system - A primer for the respiratory clinician.Paediatric respiratory reviews · 2021Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Nitric oxide (NO) is a diffusible radical gas produced from the activity of nitric oxide synthase (NOS). NOS activity in murine macrophages has a protective role against mycobacteria through generation of reactive nitrogen intermediates (RNIs). However, the production of NO by human macrophages has remained unclear due to the lack of sensitive reagents to detect NO directly. The purpose of this study was to investigate NO production and the consequence to mycobacteria in primary human macrophages. We found that Mycobacterium bovis BCG or Mycobacterium tuberculosis infection of human macrophages induced expression of NOS2 and NOS3 that resulted in detectable production of NO. Treatment with gamma interferon (IFN-γ), l-arginine, and tetrahydrobiopterin enhanced expression of NOS2 and NOS3 isoforms, as well as NO production. Both of these enzymes were shown to contribute to NO production. The maximal level of NO produced by human macrophages was not bactericidal or bacteriostatic to M. tuberculosis or BCG. The number of viable mycobacteria was increased in macrophages that produced NO, and this requires expression of nitrate reductase. An narG mutant of M. tuberculosis persisted but was unable to grow in human macrophages. Taken together, these data (i) enhance our understanding of primary human macrophage potential to produce NO, (ii) demonstrate that the level of RNIs produced in response to IFN-γ in vitro is not sufficient to limit intracellular mycobacterial growth, and (iii) suggest that mycobacteria may use RNIs to enhance their survival in human macrophages.
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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.