ArticleThe Journal of clinical investigation2010
Serine protease activity contributes to control of Mycobacterium tuberculosis in hypoxic lung granulomas in mice.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Systematic review of innate immune responses againstFrontiers in immunology · 2024Pooled it
- Elucidation of a Human Urine Metabolite as a Seryl-Leucine Glycopeptide and as a Biomarker of Effective Anti-Tuberculosis Therapy.ACS infectious diseases · 2019Trial
- Extracellular matrix and proteolysis: mechanisms driving irreversible changes and shaping cell behavior.The FEBS journal · 2026Review
- Review
- Mouse models of tuberculosis uniformly featuring hypoxic necrotic lesions and poor response to chemotherapy.Infection and immunity · 2026Article
- Mouse Models Uniformly Featuring Human-like Lesions Harboring Drug-tolerantbioRxiv : the preprint server for biology · 2025Article
- Dysplastic lung repair fosters a tuberculosis-promoting microenvironment through maladaptive macrophage polarization.PLoS pathogens · 2025Article
- Intradermal Inoculation of Mycobacterium avium in the Mouse Ear.Journal of visualized experiments : JoVE · 2025Article
- Aberrant macrophage activation and maladaptive lung repair promote tuberculosis progression uniquely in the lung.bioRxiv : the preprint server for biology · 2025Article
- Microenvironments of tuberculous granuloma: advances and opportunities for therapy.Frontiers in immunology · 2025Review
- Cytosolic serpins act in a cytoprotective feedback loop that limits ESX-1-dependent death ofmBio · 2024Article
- Imaging the Architecture of Granulomas Induced by Mycobacterium tuberculosis Infection with Single-molecule Fluorescence In Situ Hybridization.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Neutrophils insert elastase into hepatocytes to regulate calcium signaling in alcohol-associated hepatitis.The Journal of clinical investigation · 2024Article
- Ascorbic acid as serine protease inhibitor in lung cancer cell line and human serum albumin.PloS one · 2024Article
- Role of phagocyte extracellular traps duringFrontiers in microbiology · 2023Review
- Lysoptosis is an evolutionarily conserved cell death pathway moderated by intracellular serpins.Communications biology · 2022Article
- In the Thick of It: Formation of the Tuberculous Granuloma and Its Effects on Host and Therapeutic Responses.Frontiers in immunology · 2022Review
- Spatial localization of cathepsins: Implications in immune activation and resolution during infections.Frontiers in immunology · 2022Review
- Article
- Article
3 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
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The hallmark of human Mycobacterium tuberculosis infection is the presence of lung granulomas. Lung granulomas can have different phenotypes, with caseous necrosis and hypoxia present within these structures during active tuberculosis. Production of NO by the inducible host enzyme NOS2 is a key antimycobacterial defense mechanism that requires oxygen as a substrate; it is therefore likely to perform inefficiently in hypoxic regions of granulomas in which M. tuberculosis persists. Here we have used Nos2-/- mice to investigate host-protective mechanisms within hypoxic granulomas and identified a role for host serine proteases in hypoxic granulomas in determining outcome of disease. Nos2-/- mice reproduced human-like granulomas in the lung when infected with M. tuberculosis in the ear dermis. The granulomas were hypoxic and contained large amounts of the serine protease cathepsin G and clade B serine protease inhibitors (serpins). Extrinsic inhibition of serine protease activity in vivo resulted in distorted granuloma structure, extensive hypoxia, and increased bacterial growth in this model. These data suggest that serine protease activity acts as a protective mechanism within hypoxic regions of lung granulomas and present a potential new strategy for the treatment of tuberculosis.
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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.