ArticlePloS one2013
Human granuloma in vitro model, for TB dormancy and resuscitation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
102 citing papers in PubMed, 1 synthesis or guideline pooled it, 205 citations in OpenAlex.
- Pooled it
- The Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering the Immune Responses againstBiomolecular concepts · 2021Trial
- Effects of Oral Liposomal Glutathione in Altering the Immune Responses AgainstFrontiers in cellular and infection microbiology · 2021Trial
- The Synergistic Effects of the Glutathione Precursor, NAC and First-Line Antibiotics in the Granulomatous Response AgainstFrontiers in immunology · 2018Trial
- Rv2656c: A Potential Candidate Antigen Associated with Latent Tuberculosis Infection.Vaccines · 2026Article
- The 3D landscape of infection: spatial organization andFrontiers in immunology · 2026Review
- Human organoids and organ-on-chip systems for AI-guided therapeutic discovery against emerging and re-emerging infections.Frontiers in pharmacology · 2026Review
- Methodology for a freshly engineered or cryo-preserved 3D tuberculoma bioplatform for studying tuberculosis biology and high-content screening of therapeutics.Frontiers in immunology · 2026Article
- Exploring the Protein Landscape of Dormant Mycobacterium tuberculosis Through In Vitro Functional Studies.Advances in experimental medicine and biology · 2026Review
- Novel Multistage SubunitVaccines · 2025Article
- Restriction of mitochondrial oxidation of glutamine or fatty acids enhances intracellular growth ofVirulence · 2025Article
- Modeling immune responses of cattle tomSphere · 2025Article
- Methods for Evaluating the Effects of 2D and 3D Culture Environment on Macrophage Response to Mycobacterium Infection.Microorganisms · 2025Article
- Granulysin Antimicrobial Activity Promotes Dormancy in Mycobacterium tuberculosis.European journal of immunology · 2025Article
- 3D spheroid model reveals enhanced efficacy of mannose-decorated nanoparticles for TB treatment.Nanomedicine (London, England) · 2025Article
- Soluble immune mediators orchestrate protectiveeLife · 2025Article
- 3D Hydrogel Culture System Recapitulates Key Tuberculosis Phenotypes and Demonstrates Pyrazinamide Efficacy.Advanced healthcare materials · 2025Article
- Experimental dissection of tuberculosis protective immunity: a human perspective.Frontiers in cellular and infection microbiology · 2025Review
- Microenvironments of tuberculous granuloma: advances and opportunities for therapy.Frontiers in immunology · 2025Review
- CD14Frontiers in cellular and infection microbiology · 2025Article
42 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
6 authors at 2 institutions in 1 country.
Funding
Abstract
Tuberculosis (TB) is responsible for death of nearly two million people in the world annually. Upon infection, Mycobacterium tuberculosis (Mtb) causes formation of granuloma where the pathogen goes into dormant state and can live for decades before resuscitation to develop active disease when the immune system of the host is weakened and/or suppressed. In an attempt to better understand host-pathogen interactions, several groups have been developing in vitro models of human tuberculosis granuloma. However, to date, an in vitro granuloma model in which Mtb goes into dormancy and can subsequently resuscitate under conditions that mimic weakening of the immune system has not been reported. We describe the development of a biomimetic in vitro model of human tuberculosis granuloma using human primary leukocytes, in which the Mtb exhibited characteristics of dormant mycobacteria as demonstrated by (1) loss of acid-fastness, (2) accumulation of lipid bodies (3) development of rifampicin-tolerance and (4) gene expression changes. Further, when these micro granulomas were treated with immunosuppressant anti-tumor necrosis factor-alpha monoclonal antibodies (anti-TNFα mAbs), resuscitation of Mtb was observed as has been found in humans. In this human in vitro granuloma model triacylglycerol synthase 1deletion mutant (Δtgs1) with impaired ability to accumulate triacylglycerides (TG), but not the complemented mutant, could not go into dormancy. Deletion mutant of lipY, with compromised ability to mobilize the stored TG, but not the complemented mutant, was unable to come out of dormancy upon treatment with anti-TNFα mAbs. In conclusion, we have developed an in vitro human tuberculosis granuloma model that largely exhibits functional features of dormancy and resuscitation observed in human 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.