ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Microenvironments in tuberculous granulomas are delineated by distinct populations of macrophage subsets and expression of nitric oxide synthase and arginase isoforms.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 230 papers, 1 of them a synthesis that pooled it.
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.
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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
230 citing papers in PubMed, 1 synthesis or guideline pooled it, 346 citations in OpenAlex.
- Pooled it
- MakingCell insight · 2026Review
- Direct bacterial transcript visualization illuminates spatiotemporal environmental adaptation ofScience advances · 2026Article
- γδ T Cells at the Crossroads of Tuberculosis and COPD: From Early Immunity to Tissue Remodeling.International journal of molecular sciences · 2026Review
- The study of immunological markers in tuberculosis across animal models and its translation to human research.Lab animal · 2026Review
- Rifabutin boosts rifampicin accumulation in THP-1-derived M2 macrophages by inhibiting P-glycoprotein efflux activity.Archives of toxicology · 2026Article
- Co-infection of Mycobacterium tuberculosis complex and carbapenem-resistant hypervirulent Klebsiella pneumoniae in captive Asiatic black bears: a case report.BMC veterinary research · 2026Article
- Granuloma dual RNA-seq reveals composite transcriptional programs driven by neutrophils and necrosis within tuberculous granulomas.Science advances · 2026Article
- Species-specific iNOS expression distinguishes epithelial and myeloid IFNγ responses in tuberculosis.bioRxiv : the preprint server for biology · 2026Article
- From granulomas to tumors: post-tuberculosis immune and structural lung remodeling as a driver of carcinogenesis.Frontiers in immunology · 2026Review
- Macrophage states and polarization duringFrontiers in cellular and infection microbiology · 2026Review
- Arginine Metabolism in Decidual Macrophages During Pregnancy.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025Review
- Modeling immune responses of cattle tomSphere · 2025Article
- Article
- Influence of Paratuberculosis Vaccination on the Local Immune Response in Experimentally Infected Calves: An Immunohistochemical Analysis.Animals : an open access journal from MDPI · 2025Article
- Review
- Distinguishing multiple roles of T cell and macrophage involvement in determining lymph node fates during Mycobacterium tuberculosis infection.PLoS computational biology · 2025Article
- Zinc-limitedInfection and immunity · 2025Article
- Building Spatiotemporal Understanding ofACS infectious diseases · 2025Review
- 3D Hydrogel Culture System Recapitulates Key Tuberculosis Phenotypes and Demonstrates Pyrazinamide Efficacy.Advanced healthcare materials · 2025Article
170 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
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Macrophages in granulomas are both antimycobacterial effector and host cell for Mycobacterium tuberculosis, yet basic aspects of macrophage diversity and function within the complex structures of granulomas remain poorly understood. To address this, we examined myeloid cell phenotypes and expression of enzymes correlated with host defense in macaque and human granulomas. Macaque granulomas had upregulated inducible and endothelial NO synthase (iNOS and eNOS) and arginase (Arg1 and Arg2) expression and enzyme activity compared with nongranulomatous tissue. Immunohistochemical analysis indicated macrophages adjacent to uninvolved normal tissue were more likely to express CD163, whereas epithelioid macrophages in regions where bacteria reside strongly expressed CD11c, CD68, and HAM56. Calprotectin-positive neutrophils were abundant in regions adjacent to caseum. iNOS, eNOS, Arg1, and Arg2 proteins were identified in macrophages and localized similarly in granulomas across species, with greater eNOS expression and ratio of iNOS/Arg1 expression in epithelioid macrophages as compared with cells in the lymphocyte cuff. iNOS, Arg1, and Arg2 expression in neutrophils was also identified. The combination of phenotypic and functional markers support that macrophages with anti-inflammatory phenotypes localized to outer regions of granulomas, whereas the inner regions were more likely to contain macrophages with proinflammatory, presumably bactericidal, phenotypes. Together, these data support the concept that granulomas have organized microenvironments that balance antimicrobial anti-inflammatory responses to limit pathology in the lungs.
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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.