ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Multiscale computational modeling reveals a critical role for TNF-α receptor 1 dynamics in tuberculosis granuloma formation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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109 citing papers in PubMed, 169 citations in OpenAlex.
- A Comparison of Mechanisms Driving Lesion Outcomes During Lung Tumor and Tuberculosis Granuloma Formation.Bulletin of mathematical biology · 2026Article
- Review
- The eight pillars of within-host tuberculosis modelling.Frontiers in immunology · 2026Review
- Global trends and hotspots of tumor necrosis factor-alpha in pulmonary tuberculosis: a bibliometric and visualization analysis.Journal of thoracic disease · 2025Article
- Partially-functional exhausted CD8+ T cells can contribute to short-term viral suppression: a computational prediction for children with perinatal HIV.bioRxiv : the preprint server for biology · 2025Article
- A novel machine-learning based optimization: identifying new treatment regimens for tuberculosis.Numerical algebra, control and optimization · 2025Article
- Xenobiotic Toxicants and Particulate Matter: Effects, Mechanisms, Impacts on Human Health, and Mitigation Strategies.Journal of xenobiotics · 2025Review
- Timing matters in macrophage/CD4+ T cell interactions: an agent-based model comparingmSystems · 2025Article
- Uptake of Biomimetic Nanovesicles by Granuloma for Photodynamic Therapy of Tuberculosis.ACS omega · 2025Article
- GEODE: anFrontiers in pharmacology · 2025Article
- In silico agent-based modeling approach to characterize multiple in vitro tuberculosis infection models.PloS one · 2024Article
- A brief overview of mathematical modeling of the within-host dynamics of Mycobacterium tuberculosis.Frontiers in applied mathematics and statistics · 2024Article
- Alveolar deposition of inhaled fine particulate matter increased risk of severity of pulmonary tuberculosis in the upper and middle lobes.ERJ open research · 2023Article
- Optimizing tuberculosis treatment efficacy: Comparing the standard regimen with Moxifloxacin-containing regimens.PLoS computational biology · 2023Article
- Active tuberculosis in inflammatory bowel disease patients: a case-control study.Therapeutic advances in gastroenterology · 2023Article
- Automated quantitative assay of fibrosis characteristics in tuberculosis granulomas.Frontiers in microbiology · 2023Article
- Vaccine-Induced Subcutaneous Granulomas in Goats Reflect Differences in Host-Mycobacterium Interactions between BCG- and Recombinant BCG-Derivative Vaccines.International journal of molecular sciences · 2022Article
- Review article: latent tuberculosis in patients with inflammatory bowel diseases receiving immunosuppression-risks, screening, diagnosis and management.Alimentary pharmacology & therapeutics · 2022Review
- Building digital twins of the human immune system: toward a roadmap.NPJ digital medicine · 2022Review
- A virtual host model of Mycobacterium tuberculosis infection identifies early immune events as predictive of infection outcomes.Journal of theoretical biology · 2022Article
49 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Multiple immune factors control host responses to Mycobacterium tuberculosis infection, including the formation of granulomas, which are aggregates of immune cells whose function may reflect success or failure of the host to contain infection. One such factor is TNF-α. TNF-α has been experimentally characterized to have the following activities in M. tuberculosis infection: macrophage activation, apoptosis, and chemokine and cytokine production. Availability of TNF-α within a granuloma has been proposed to play a critical role in immunity to M. tuberculosis. However, in vivo measurement of a TNF-α concentration gradient and activities within a granuloma are not experimentally feasible. Further, processes that control TNF-α concentration and activities in a granuloma remain unknown. We developed a multiscale computational model that includes molecular, cellular, and tissue scale events that occur during granuloma formation and maintenance in lung. We use our model to identify processes that regulate TNF-α concentration and cellular behaviors and thus influence the outcome of infection within a granuloma. Our model predicts that TNF-αR1 internalization kinetics play a critical role in infection control within a granuloma, controlling whether there is clearance of bacteria, excessive inflammation, containment of bacteria within a stable granuloma, or uncontrolled growth of bacteria. Our results suggest that there is an interplay between TNF-α and bacterial levels in a granuloma that is controlled by the combined effects of both molecular and cellular scale processes. Finally, our model elucidates processes involved in immunity to M. tuberculosis that may be new targets for therapy.
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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.