ArticlePLoS computational biology2010
Identification of key processes that control tumor necrosis factor availability in a tuberculosis granuloma.
Article in PLoS computational biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 57 citations in OpenAlex.
- Distinct mechanisms drive post-antibiotic Tuberculosis relapse post-cure versus post-treatment-failure.bioRxiv : the preprint server for biology · 2026Article
- Rankings of tuberculosis antibiotic treatment regimens are sensitive to spatial scale, detection limit, and initial host bacterial burden.Journal of theoretical biology · 2025Article
- Role of Tumor Necrosis Factor in Tuberculosis.Biomolecules · 2025Review
- Artemisinin and its derivatives: all-rounders that may prevent the progression from lung injury to lung cancer.Frontiers in pharmacology · 2025Review
- Mathematical model of oxygen, nutrient, and drug transport in tuberculosis granulomas.PLoS computational biology · 2024Article
- In silico agent-based modeling approach to characterize multiple in vitro tuberculosis infection models.PloS one · 2024Article
- Tuberculosis and TNF-α inhibitors in children: how to manage a fine balance.Acta bio-medica : Atenei Parmensis · 2020Article
- Modeling immune cell behavior across scales in cancer.Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- Tumor necrosis factor-mediated disposition of infliximab in ulcerative colitis patients.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- Agent-based models of inflammation in translational systems biology: A decade later.Wiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- Multiscale Coupling of an Agent-Based Model of Tissue Fibrosis and a Logic-Based Model of Intracellular Signaling.Frontiers in physiology · 2019Article
- The Role of Dimensionality in Understanding Granuloma Formation.Computation (Basel, Switzerland) · 2018Article
- Low Levels of T Cell Exhaustion in Tuberculous Lung Granulomas.Infection and immunity · 2018Article
- Dynamic balance of pro- and anti-inflammatory signals controls disease and limits pathology.Immunological reviews · 2018Review
- Identifying mechanisms driving formation of granuloma-associated fibrosis during Mycobacterium tuberculosis infection.Journal of theoretical biology · 2017Article
- A review of computational and mathematical modeling contributions to our understanding of Mycobacterium tuberculosis within-host infection and treatment.Current opinion in systems biology · 2017Article
- Deletion of TGF-β1 Increases Bacterial Clearance by Cytotoxic T Cells in a Tuberculosis Granuloma Model.Frontiers in immunology · 2017Article
- A Multi-Compartment Hybrid Computational Model Predicts Key Roles for Dendritic Cells in Tuberculosis Infection.Computation (Basel, Switzerland) · 2016Article
- Lung necrosis and neutrophils reflect common pathways of susceptibility to Mycobacterium tuberculosis in genetically diverse, immune-competent mice.Disease models & mechanisms · 2015Article
- A population model capturing dynamics of tuberculosis granulomas predicts host infection outcomes.Mathematical biosciences and engineering : MBE · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Tuberculosis (TB) granulomas are organized collections of immune cells comprised of macrophages, lymphocytes and other cells that form in the lung as a result of immune response to Mycobacterium tuberculosis (Mtb) infection. Formation and maintenance of granulomas are essential for control of Mtb infection and are regulated in part by a pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF). To characterize mechanisms that control TNF availability within a TB granuloma, we developed a multi-scale two compartment partial differential equation model that describes a granuloma as a collection of immune cells forming concentric layers and includes TNF/TNF receptor binding and trafficking processes. We used the results of sensitivity analysis as a tool to identify experiments to measure critical model parameters in an artificial experimental model of a TB granuloma induced in the lungs of mice following injection of mycobacterial antigen-coated beads. Using our model, we then demonstrated that the organization of immune cells within a TB granuloma as well as TNF/TNF receptor binding and intracellular trafficking are two important factors that control TNF availability and may spatially coordinate TNF-induced immunological functions within a granuloma. Further, we showed that the neutralization power of TNF-neutralizing drugs depends on their TNF binding characteristics, including TNF binding kinetics, ability to bind to membrane-bound TNF and TNF binding stoichiometry. To further elucidate the role of TNF in the process of granuloma development, our modeling and experimental findings on TNF-associated molecular scale aspects of the granuloma can be incorporated into larger scale models describing the immune response to TB infection. Ultimately, these modeling and experimental results can help identify new strategies for TB disease control/therapy.
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