ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Human TOLLIP regulates TLR2 and TLR4 signaling and its polymorphisms are associated with susceptibility to tuberculosis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 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.
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Who cites it
81 citing papers in PubMed, 2 syntheses or guidelines pooled it, 145 citations in OpenAlex.
- Associations between genetic variants of Toll-interacting proteins and interstitial lung diseases: a systematic review and meta-analysis.Orphanet journal of rare diseases · 2024Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Porcelain-clay-inspired microsphere hydrogel bioink facilitates bone regeneration via immune-osteogenic regulation.Bioactive materials · 2027Article
- Immune system expression profiling in patients experiencing low back pain: A pilot study.PM & R : the journal of injury, function, and rehabilitation · 2026Observational
- Comprehensive single-cell RNA-sequencing study of Tollip deficiency effect in IL-13-stimulated human airway epithelial cells.BMC research notes · 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
- BCG and beyond: unlocking new frontiers in TB vaccine development.Frontiers in immunology · 2025Review
- Article
- Human Alveolar and Monocyte-Derived Human Macrophage Responses to Mycobacterium tuberculosis.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- TOLLIP inhibits lipid accumulation and the integrated stress response in alveolar macrophages to control Mycobacterium tuberculosis infection.Nature microbiology · 2024Article
- Genetic history of Cambridgeshire before and after the Black Death.Science advances · 2024Article
- Genetic Underpinnings of Pulmonary Fibrosis: An Overview.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- Toll-interacting protein may affect doxorubicin resistance in hepatocellular carcinoma cell lines.Molecular biology reports · 2023Article
- MUC5AC Genetic Variation Is Associated With Tuberculous Meningitis Cerebral Spinal Fluid Cytokine Responses and Mortality.The Journal of infectious diseases · 2023Article
- Tuberculosis severity associates with variants and eQTLs related to vascular biology and infection-induced inflammation.PLoS genetics · 2023Article
- Hotspots and Frontiers of Host Immune Response in Idiopathic Pulmonary Fibrosis: A Bibliometric and Scientific Visual Research from 2000 to 2022.Journal of immunology research · 2023Article
- Design and rationale for the prospective treatment efficacy in IPF using genotype for NAC selection (PRECISIONS) clinical trial.BMC pulmonary medicine · 2022Article
- Autophagopathies: from autophagy gene polymorphisms to precision medicine for human diseases.Autophagy · 2022Article
- Suppression of ACE2 SUMOylation protects against SARS-CoV-2 infection through TOLLIP-mediated selective autophagy.Nature communications · 2022Article
- TOLLIP Optimizes Dendritic Cell Maturation to Lipopolysaccharide andJournal of immunology (Baltimore, Md. : 1950) · 2022Article
21 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
8 authors at 5 institutions in 4 countries.
Funding
Abstract
Tuberculosis, one of the leading causes of death worldwide, stimulates inflammatory responses with beneficial and pathologic consequences. The regulation and nature of an optimal inflammatory response to Mycobacterium tuberculosis remains poorly understood in humans. Insight into mechanisms of negative regulation of the TLR-mediated innate immune response to M. tuberculosis could provide significant breakthroughs in the design of new vaccines and drugs. We hypothesized that TOLLIP and its common variants negatively regulate TLR signaling in human monocytes and are associated with susceptibility to tuberculosis. Using short hairpin RNA knockdown of TOLLIP in peripheral blood human monocytes, we found that TOLLIP suppresses TNF and IL-6 production after stimulation with TLR2 and TLR4 ligands. In contrast, secretion of the anti-inflammatory cytokine IL-10 was induced by TOLLIP. We also discovered two common polymorphisms that are associated with either decreased levels of mRNA expression (rs3750920) or increased IL-6 production (rs5743899) in a sample of 56 healthy volunteers. Furthermore, in a case-population study in Vietnam with 760 cord blood samples and 671 TB case patients, we found that SNPs rs3750920 and rs5743899 were associated with susceptibility to tuberculosis (p = 7.03 × 10(-16) and 6.97 × 10(-7), respectively). These data demonstrate that TOLLIP has an anti-inflammatory effect on TLR signaling in humans and that TOLLIP deficiency is associated with an increased risk of tuberculosis. To our knowledge, these data also show the first associations of TOLLIP polymorphisms with any infectious disease. These data also implicate an unexpected mechanism of negative regulation of TLR signaling in human tuberculosis pathogenesis.
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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.