ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Computational modeling predicts IL-10 control of lesion sterilization by balancing early host immunity-mediated antimicrobial responses with caseation during mycobacterium tuberculosis infection.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 74 citations in OpenAlex.
- A Comparison of Mechanisms Driving Lesion Outcomes During Lung Tumor and Tuberculosis Granuloma Formation.Bulletin of mathematical biology · 2026Article
- Age-related severity of nontuberculous mycobacterial lung disease is mediated by aberrant macrophage responses and lung microbial dysbiosis.The Journal of infection · 2025Article
- Rankings of tuberculosis antibiotic treatment regimens are sensitive to spatial scale, detection limit, and initial host bacterial burden.Journal of theoretical biology · 2025Article
- Timing matters in macrophage/CD4+ T cell interactions: an agent-based model comparingmSystems · 2025Article
- Evaluation of the Anti-Mycobacterial and Anti-Inflammatory Activities of the New Cardiotonic Steroid γ-Benzylidene Digoxin-15 in Macrophage Models of Infection.Microorganisms · 2025Article
- CD4Immunity · 2024Article
- Characterizing the immune response toFrontiers in immunology · 2024Review
- In silico agent-based modeling approach to characterize multiple in vitro tuberculosis infection models.PloS one · 2024Article
- A virtual host model of Mycobacterium tuberculosis infection identifies early immune events as predictive of infection outcomes.Journal of theoretical biology · 2022Article
- IL-10 Receptor Blockade Delivered Simultaneously with Bacillus Calmette-Guérin Vaccination Sustains Long-Term Protection againstJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- In the Thick of It: Formation of the Tuberculous Granuloma and Its Effects on Host and Therapeutic Responses.Frontiers in immunology · 2022Review
- A multi-scale pipeline linking drug transcriptomics with pharmacokinetics predicts in vivo interactions of tuberculosis drugs.Scientific reports · 2021Article
- Article
- Neutrophil Dynamics AffectFrontiers in immunology · 2021Article
- A computational model tracks whole-lung Mycobacterium tuberculosis infection and predicts factors that inhibit dissemination.PLoS computational biology · 2020Article
- IL-10 Impairs Local Immune Response in Lung Granulomas and Lymph Nodes during EarlyJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- An Agent-Based Systems Pharmacology Model of the Antibody-Drug Conjugate Kadcyla to Predict Efficacy of Different Dosing Regimens.The AAPS journal · 2020Article
- Data-Driven Model Validation Across Dimensions.Bulletin of mathematical biology · 2019Article
- The Role of Dimensionality in Understanding Granuloma Formation.Computation (Basel, Switzerland) · 2018Article
- Correlative analysis of the expression of IL-10 and Ki-67 in human cervical cancer and cervical intraepithelial neoplasias and human papillomavirus infection.Oncology letters · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Although almost a third of the world's population is infected with the bacterial pathogen Mycobacterium tuberculosis, our understanding of the functions of many immune factors involved in fighting infection is limited. Determining the role of the immunosuppressive cytokine IL-10 at the level of the granuloma has proven difficult because of lesional heterogeneity and the limitations of animal models. In this study, we take an in silico approach and, through a series of virtual experiments, we predict several novel roles for IL-10 in tuberculosis granulomas: 1) decreased levels of IL-10 lead to increased numbers of sterile lesions, but at the cost of early increased caseation; 2) small increases in early antimicrobial activity cause this increased lesion sterility; 3) IL-10 produced by activated macrophages is a major mediator of early antimicrobial activity and early host-induced caseation; and 4) increasing levels of infected macrophage derived IL-10 promotes bacterial persistence by limiting the early antimicrobial response and preventing lesion sterilization. Our findings, currently only accessible using an in silico approach, suggest that IL-10 at the individual granuloma scale is a critical regulator of lesion outcome. These predictions suggest IL-10-related mechanisms that could be used as adjunctive therapies during 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.