ArticleThe Journal of clinical investigation2009
TLR9 regulates the mycobacteria-elicited pulmonary granulomatous immune response in mice through DC-derived Notch ligand delta-like 4.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 125 citations in OpenAlex.
- Early Notch signals from fibroblastic reticular cells program effector CD8+ T cell differentiation.The Journal of experimental medicine · 2025Article
- Toll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2025Article
- Another Notch in the Belt of Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2024Review
- Canonical notch activation in patients with scrub typhus: association with organ dysfunction and poor outcome.Infection · 2024Article
- Upregulation of Notch Signaling and Cell-Differentiation Inhibitory Transcription Factors in Stable Chronic Obstructive Pulmonary Disease Patients.International journal of molecular sciences · 2024Article
- Activation of host nucleic acid sensors byCritical reviews in microbiology · 2024Review
- Notch Signaling Regulates the Function and Phenotype of Dendritic Cells inMicroorganisms · 2023Article
- Notch Signaling Pathway Promotes Th17 Cell Differentiation and Participates in Thyroid Autoimmune Injury in Experimental Autoimmune Thyroiditis Mice.Mediators of inflammation · 2023Article
- Notch signaling pathway involved inFrontiers in cellular and infection microbiology · 2023Article
- Article
- A narrative review of the role of the Notch signaling pathway in rheumatoid arthritis.Annals of translational medicine · 2022Review
- Excessive Activation of Notch Signaling in Macrophages Promote Kidney Inflammation, Fibrosis, and Necroptosis.Frontiers in immunology · 2022Article
- Sensing of mycobacterial arabinogalactan by galectin-9 exacerbates mycobacterial infection.EMBO reports · 2021Article
- Notch signaling pathway in infectious diseases: role in the regulation of immune response.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Review
- NOTCH1 and DLL4 are involved in the human tuberculosis progression and immune response activation.Tuberculosis (Edinburgh, Scotland) · 2020Article
- Notch-1 Signaling Modulates Macrophage Polarization and Immune Defense againstMicroorganisms · 2020Article
- Review
- Notch signalling in T cell homeostasis and differentiation.Open biology · 2019Review
- Multi-Faceted Notch in Allergic Airway Inflammation.International journal of molecular sciences · 2019Review
- Dynamic balance of pro- and anti-inflammatory signals controls disease and limits pathology.Immunological reviews · 2018Review
6 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 3 institutions in 1 country.
Funding
Abstract
TLR9 activation is important for the maintenance of mycobacteria-elicited pulmonary granulomatous responses, hallmarks of protective immune responses following mycobacterial infection. However, the mechanism or mechanisms underlying this effect of TLR9 are not clear. Here, we show that Tlr9-deficient mice challenged with a Mycobacterium antigen display an altered Th17 cytokine profile, decreased accumulation of granuloma-associated myeloid DCs, and profoundly impaired delta-like 4 (dll4) Notch ligand expression. Mechanistic analysis revealed that WT bone marrow-derived DCs but not macrophages promoted the differentiation of Th17 cells from bacillus Calmette-Guérin-challenged (BCG-challenged) lung CD4+ T cells. Both lung and bone marrow DCs isolated from Tlr9-deficient mice inoculated with Mycobacterium antigen expressed lower levels of dll4 Notch ligand than the same cells isolated from WT mice. Passively immunizing WT mice with neutralizing antibodies specific for dll4 during granuloma formation resulted in larger granulomas and lower levels of Th17-related cytokines. In addition, dll4 specifically regulated Th17 activation in vitro. Together, these results suggest dll4 plays an important role in promoting Th17 effector activity during a mycobacterial challenge. Furthermore, TLR9 seems to be required for optimal dll4 expression and the regulation of Mycobacterium antigen-elicited granuloma formation in mice.
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Identifiers
What OpenQuestion holds
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.