ArticleThe Journal of clinical investigation2018
Mycobacterial growth inhibition is associated with trained innate immunity.
Article in The Journal of clinical investigation, 2018. 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 104 papers, 2 of them syntheses that pooled it.
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
104 citing papers in PubMed, 2 syntheses or guidelines pooled it, 184 citations in OpenAlex.
- Development and application of the direct mycobacterial growth inhibition assay: a systematic review.Frontiers in immunology · 2024Pooled it
- Whole Blood Mycobacterial Growth Assays for Assessing Human Tuberculosis Susceptibility: A Systematic Review and Meta-Analysis.Frontiers in immunology · 2021Pooled it
- Induction of Functional Specific Antibodies, IgG-Secreting Plasmablasts and Memory B Cells Following BCG Vaccination.Frontiers in immunology · 2021Trial
- Neonatal BCG Vaccination Reduces Interferon-γ Responsiveness to Heterologous Pathogens in Infants From a Randomized Controlled Trial.The Journal of infectious diseases · 2020Trial
- Single-cell transcriptomics reveal PD-1-loss-driven immune dysregulation of pulmonary lymphocytes during earlyMicrobiology spectrum · 2026Article
- Trained immunity: new paradigm in the immunological memory of cardiovascular disease.ImmunoHorizons · 2026Review
- Antibodies in tuberculosis: functional capacity as key determinant.Infection and immunity · 2026Review
- In vitro protocol demonstrating five functional steps of trained immunity in mice: Implications on biomarker discovery and translational research.Cell reports · 2025Article
- Nucleotide-Binding Oligomerization Domain 2 in Signaling, Immunity, and Mycobacterial Infection.Immunity, inflammation and disease · 2025Review
- Host-intrinsic and host-extrinsic factors modulate immunity to Mtb infection, reinfection, and noncanonical vaccination routes.Cell reports. Medicine · 2025Review
- Immunization with Complete Freund's Adjuvant Reveals Trained Immunity-like Features in A/J Mice.Vaccines · 2025Article
- Trained immunity in chronic inflammatory diseases and cancer.Nature reviews. Immunology · 2025Review
- Sera contributing to mycobacterial growth restrictioniScience · 2025Article
- Identification of inflammatory protein biomarkers for predicting the different subtype of adult with tuberculosis: an Olink proteomic study.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Soluble immune mediators orchestrate protectiveeLife · 2025Article
- Timing matters in macrophage/CD4+ T cell interactions: an agent-based model comparingmSystems · 2025Article
- Early and delayed STAT1-dependent responses drive local trained immunity of macrophages in the spleen.eLife · 2025Article
- PBMC transcriptomic signatures reflect Trypanosoma cruzi strain diversity and trained immunity in chronically infected macaques.JCI insight · 2025Article
- Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia.Nature communications · 2025Article
- Mycobacterium tuberculosis growth inhibition by peripheral blood mononuclear cells from household contacts is not affected by previous SARS-CoV-2 infection.Gates open research · 2025Article
44 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
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The lack of defined correlates of protection hampers development of vaccines against tuberculosis (TB). In vitro mycobacterial outgrowth assays are thought to better capture the complexity of the human host/Mycobacterium tuberculosis (Mtb) interaction. Here, we used a mycobacterial growth inhibition assay (MGIA) based on peripheral blood mononuclear cells to investigate the capacity to control outgrowth of bacille Calmette-Guérin (BCG). Interestingly, strong control of BCG outgrowth was observed almost exclusively in individuals with recent exposure to Mtb, but not in (long-term) latent TB infection, and only modestly in BCG vaccinees. Mechanistically, control of mycobacterial outgrowth strongly correlated with the presence of a CD14dim monocyte population, but also required the presence of T cells. The nonclassical monocytes produced CXCL10, and CXCR3 receptor blockade inhibited the capacity to control BCG outgrowth. Expression of CXCR3 splice variants was altered in recently Mtb-exposed individuals. Cytokines previously associated with trained immunity were detected in MGIA supernatants, and CXCL9, CXCL10, and CXCL11 represent new markers of trained immunity. These data indicate that CXCR3 ligands are associated with trained immunity and are critical factors in controlling mycobacterial outgrowth. In conclusion, control of mycobacterial outgrowth early after exposure to Mtb is the result of trained immunity mediated by a CXCL10-producing nonclassical CD14dim monocyte subset.
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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.