Observational studyAmerican journal of respiratory and critical care medicine2017
A Functional Toll-Interacting Protein Variant Is Associated with Bacillus Calmette-Guérin-Specific Immune Responses and Tuberculosis.
Observational study in American journal of respiratory and critical care medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- Mycobacterium tuberculosis-Specific T-Cell Responses Are Impaired During Late Pregnancy With Elevated Biomarkers of Tuberculosis Risk Postpartum.The Journal of infectious diseases · 2022Trial
- Monocyte metabolic transcriptional programs associate with resistance to tuberculin skin test/interferon-γ release assay conversion.The Journal of clinical investigation · 2021Trial
- cytoGPNet: Enhancing clinical outcome prediction accuracy using longitudinal cytometry data in small cohort studies.Patterns (New York, N.Y.) · 2025Article
- BCG induced innate immune response heterogeneity and susceptibility to pediatric tuberculosis.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Association of TOLLIP mRNA Expression and TOLLIP rs5743899A/G, TOLLIP rs3750920C/T, and IL-10 -1082G/A Single-Nucleotide Polymorphisms with Susceptibility to Tuberculosis.Current microbiology · 2025Article
- DiminishedOpen forum infectious diseases · 2025Article
- BCG and beyond: unlocking new frontiers in TB vaccine development.Frontiers in immunology · 2025Review
- TOLLIP inhibits lipid accumulation and the integrated stress response in alveolar macrophages to control Mycobacterium tuberculosis infection.Nature microbiology · 2024Article
- MUC5AC Genetic Variation Is Associated With Tuberculous Meningitis Cerebral Spinal Fluid Cytokine Responses and Mortality.The Journal of infectious diseases · 2023Article
- Host genetic background is a barrier to broadly effective vaccine-mediated protection against tuberculosis.The Journal of clinical investigation · 2023Article
- Genetic epidemiology of resistance to M. tuberculosis Infection: importance of study design and recent findings.Genes and immunity · 2023Review
- Metabolites enhance innate resistance to human Mycobacterium tuberculosis infection.JCI insight · 2022Article
- Autophagopathies: from autophagy gene polymorphisms to precision medicine for human diseases.Autophagy · 2022Article
- TOLLIP Optimizes Dendritic Cell Maturation to Lipopolysaccharide andJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- REL and BHLHE40 Variants Are Associated with IL-12 and IL-10 Responses and Tuberculosis Risk.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Sex-Specific Differences in the Clinical Profile Among Patients with Tracheobronchial Tuberculosis: A Hospital-Based Cross-Sectional Study in Shenzhen, China.International journal of general medicine · 2022Article
- Toll-Interacting Protein in Pulmonary Diseases. Abiding by the Goldilocks Principle.American journal of respiratory cell and molecular biology · 2021Review
- HDAC3 inhibitor RGFP966 controls bacterial growth and modulates macrophage signaling during Mycobacterium tuberculosis infection.Tuberculosis (Edinburgh, Scotland) · 2021Article
- Genetics and evolution of tuberculosis pathogenesis: New perspectives and approaches.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2020Review
- Nicotinamide Limits Replication of Mycobacterium tuberculosis and Bacille Calmette-Guérin Within Macrophages.The Journal of infectious diseases · 2020Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
rationaleThe molecular mechanisms that regulate tuberculosis susceptibility and bacillus Calmette-Guérin (BCG)-induced immunity are mostly unknown. However, induction of the adaptive immune response is a critical step in host control of Mycobacterium tuberculosis. Toll-interacting protein (TOLLIP) is a ubiquitin-binding protein that regulates innate immune responses, including Toll-like receptor signaling, which initiate adaptive immunity. TOLLIP variation is associated with susceptibility to tuberculosis, but the mechanism by which it regulates tuberculosis immunity is poorly understood.
objectivesTo identify functional TOLLIP variants and evaluate the role of TOLLIP variation on innate and adaptive immune responses to mycobacteria and susceptibility to tuberculosis.
methodsWe used human cellular immunology approaches to characterize the role of a functional TOLLIP variant on monocyte mRNA expression and M. tuberculosis-induced monocyte immune functions. We also examined the association of TOLLIP variation with BCG-induced T-cell responses and susceptibility to latent tuberculosis infection. MEASUREMENTS AND MAIN
resultsWe identified a functional TOLLIP promoter region single-nucleotide polymorphism, rs5743854, which was associated with decreased TOLLIP mRNA expression in infant monocytes. After M. tuberculosis infection, TOLLIP-deficient monocytes demonstrated increased IL-6, increased nitrite, and decreased bacterial replication. The TOLLIP-deficiency G/G genotype was associated with decreased BCG-specific IL-2
conclusionsTOLLIP deficiency is associated with decreased BCG-specific T-cell responses and increased susceptibility to tuberculosis. We hypothesize that the heightened antibacterial monocyte responses after vaccination of TOLLIP-deficient infants are responsible for decreased BCG-specific T-cell responses. Activating TOLLIP may provide a novel adjuvant strategy for BCG vaccination.
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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.