ArticleThe Journal of clinical investigation2020
DNA hypermethylation during tuberculosis dampens host immune responsiveness.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03941496 (Phase 1b/2a Safety and Immunogenicity of the DNMT Inhibitor Azacitidine During Anti-Tuberculosis Therapy), which is not on this map. Cited by 59 papers.
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.
Phase 1b/2a Safety and Immunogenicity of the DNMT Inhibitor Azacitidine During Anti-Tuberculosis Therapy
Who cites it
59 citing papers in PubMed, 103 citations in OpenAlex.
- BCG-Induced DNA Methylation Changes Improve Coronavirus Disease 2019 Vaccine Immunity Without Decreasing the Risk for Severe Acute Respiratory Syndrome Coronavirus 2 Infection.Open forum infectious diseases · 2025Trial
- Host-pathogen interactions in tuberculosis: from immunological mechanisms to translational applications.Cell insight · 2026Review
- Immune endotypes in tuberculosis: Keys to decoding disease complexity.Journal of internal medicine · 2026Review
- Elimination of senescent cells with senolytic drugs as adjunctive host-directed therapy reduces tuberculosis progression in mice.Nature communications · 2026Article
- Opposite effects of chronic HIV infection and antiretroviral medication on organismal and organ-specific biological aging.Nature communications · 2026Article
- Necro-mosaic: a lesion-aware framework for testing programmed cell-death-associated mechanisms in tuberculosis.Frontiers in immunology · 2026Review
- Macrophage states and polarization duringFrontiers in cellular and infection microbiology · 2026Review
- Daily intake of a lycopene-rich juice is associated with reductions in inflammatory markers but not increases in skin carotenoids in a pilot study among participants with obesity.BMC nutrition · 2025Article
- Whole Blood vs Serum-Derived Exosomes for Host and Pathogen-Specific Tuberculosis Biomarker Identification: RNA-Seq-Based Machine-Learning Approach.Biochemical genetics · 2025Article
- Proceedings from the Third International Post-Tuberculosis Symposium: expanding the circle.IJTLD open · 2025Article
- The pathway of autophagy in the epigenetic landscape ofAutophagy · 2025Review
- DNA methylation patterns associated with prior tuberculosis infection in people with HIV.Scientific reports · 2025Article
- Nutritional Deficiencies and Management in Tuberculosis: Pharmacotherapeutic and Clinical Implications.Nutrients · 2025Review
- The role of estrogen receptor α and heat shock protein 90 in the apoptosis of fish liver cells after fipronil exposure.Fish physiology and biochemistry · 2025Article
- Dynamic Alterations in DNA Methylation of CD4MedComm · 2025Article
- Crosstalk between metabolism and epigenetics during macrophage polarization.Epigenetics & chromatin · 2025Review
- Sensitivity of Immunodiagnostic Tests in Localized Versus Disseminated Tuberculosis-A Systematic Review of Individual Patient Data.Tropical medicine and infectious disease · 2025Review
- Increased autophagy activity regulated by LC3B gene promoter DNA methylation is associated with progression to active pulmonary tuberculosis disease.Respiratory research · 2025Article
- Tuberculosis and Increased Incidence of Cardiovascular Disease: Cohort Study Using United States and United Kingdom Health Records.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Article
- Characterization of Rationally Designed CRISPR/Cas9-Based DNA Methyltransferases with Distinct Methyltransferase and Gene Silencing Activities in Human Cell Lines and Primary Human T Cells.ACS synthetic biology · 2025Article
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 4 countries.
Funding
Abstract
Mycobacterium tuberculosis (M. tuberculosis) has coevolved with humans for millennia and developed multiple mechanisms to evade host immunity. Restoring host immunity in order to improve outcomes and potentially shorten existing therapy will require identification of the full complement by which host immunity is inhibited. Perturbation of host DNA methylation is a mechanism induced by chronic infections such as HIV, HPV, lymphocytic choriomeningitis virus (LCMV), and schistosomiasis to evade host immunity. Here, we evaluated the DNA methylation status of patients with tuberculosis (TB) and their asymptomatic household contacts and found that the patients with TB have DNA hypermethylation of the IL-2/STAT5, TNF/NF-κB, and IFN-γ signaling pathways. We performed methylation-sensitive restriction enzyme-quantitative PCR (MSRE-qPCR) and observed that multiple genes of the IL-12/IFN-γ signaling pathway (IL12B, IL12RB2, TYK2, IFNGR1, JAK1, and JAK2) were hypermethylated in patients with TB. The DNA hypermethylation of these pathways was associated with decreased immune responsiveness with decreased mitogen-induced upregulation of IFN-γ, TNF, IL-6, CXCL9, CXCL10, and IL-1β production. The DNA hypermethylation of the IL-12/IFN-γ pathway was associated with decreased IFN-γ-induced gene expression and decreased IL-12-inducible upregulation of IFN-γ. This study demonstrates that immune cells from patients with TB are characterized by DNA hypermethylation of genes critical to mycobacterial immunity resulting in decreased mycobacteria-specific and nonspecific immune responsiveness.
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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.