ArticleInvestigative ophthalmology & visual science2009
Nucleotide oligomerization domain-2 (NOD2)-induced uveitis: dependence on IFN-gamma.
Article in Investigative ophthalmology & visual science, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Review
- Immunological analysis of Blau syndrome, a unique autoinflammatory state.Frontiers in immunology · 2026Review
- Vertical transmission of Leishmania donovani with placental degeneration in the pregnant mouse model of visceral leishmaniasis.PLoS neglected tropical diseases · 2025Article
- NOD-like receptors in fish: evolution, structure, immune signaling, and targeting for aquaculture vaccine adjuvants.Frontiers in immunology · 2025Review
- NOD2 activation enhances macrophage Fcγ receptor function and may increase the efficacy of antibody therapy.Frontiers in immunology · 2024Article
- Teleost NOD-like receptors and their downstream signaling pathways: A brief review.Fish and shellfish immunology reports · 2022Review
- Targeting interferon-γ in hyperinflammation: opportunities and challenges.Nature reviews. Rheumatology · 2021Review
- Research Progress on the Mechanism of Natural Product Ingredients in the Treatment of Uveitis.Journal of immunology research · 2021Review
- Phenotypic Differences in Primary Murine Microglia Treated with NOD1, NOD2, and NOD1/2 Agonists.Journal of molecular neuroscience : MN · 2020Article
- Interferon gamma boosts the nucleotide oligomerization domain 2-mediated signaling pathway in human dendritic cells in an X-linked inhibitor of apoptosis protein and mammalian target of rapamycin-dependent manner.Cellular & molecular immunology · 2017Article
- Characterization of Rabbit Nucleotide-Binding Oligomerization Domain 1 (NOD1) and the Role of NOD1 Signaling Pathway during Bacterial Infection.Frontiers in immunology · 2017Article
- The common NOD2/CARD15 variant P268S in patients with non-infectious uveitis: a cohort study.Pediatric rheumatology online journal · 2015Article
- NOD1 and NOD2 receptors in mrigal (Cirrhinus mrigala): inductive expression and downstream signalling in ligand stimulation and bacterial infections.Journal of biosciences · 2013Article
- Identification of MDP (muramyl dipeptide)-binding key domains in NOD2 (nucleotide-binding and oligomerization domain-2) receptor of Labeo rohita.Fish physiology and biochemistry · 2013Article
- NOD2 signaling contributes to host defense in the lungs against Escherichia coli infection.Infection and immunity · 2012Article
- Toll-like receptor 2 ligand pretreatment attenuates retinal microglial inflammatory response but enhances phagocytic activity toward Staphylococcus aureus.Infection and immunity · 2012Article
- MDP up-regulates the gene expression of type I interferons in human aortic endothelial cells.Molecules (Basel, Switzerland) · 2012Article
- Retinal astrocytes pretreated with NOD2 and TLR2 ligands activate uveitogenic T cells.PloS one · 2012Article
- NLRs in immune privileged sites.Current opinion in pharmacology · 2011Review
- Endotoxin-induced uveitis is primarily dependent on radiation-resistant cells and on MyD88 but not TRIF.Journal of leukocyte biology · 2011Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
purposeNucleotide oligomerization domain-2 (NOD2) plays an important role in innate immunity to sense muramyl dipeptide (MDP), a component of bacterial cell walls. Notably, NOD2 is linked to eye inflammation because mutations in NOD2 cause a granulomatous type of uveitis called Blau syndrome. A mouse model of NOD2-dependent ocular inflammation was employed to test the role of a cytokine strongly implicated in granuloma formation, IFN-gamma, in order to gain insight into downstream functional consequences of NOD2 activation within the eye triggering uveitis.
methodsMice deficient in IFN-gamma, NOD2, or CD11b and their wild-type controls were treated with intravitreal injection of MDP in the presence or absence of IFN-gamma. IFN-gamma production in the eye was measured by ELISA. The intravascular inflammatory response within the iris was quantified by intravital microscopy.
resultsNOD2 activation resulted in the production of IFN-gamma within the eye. Deficiency in IFN-gamma diminished the development of MDP-induced uveitis, indicating its crucial role in downstream inflammatory events triggered by NOD2. Moreover, exogenous IFN-gamma markedly exacerbated MDP-induced ocular inflammation in a NOD2-dependent mechanism. The potential of IFN-gamma to enhance inflammation required the adhesion molecule CD11b because CD11b-deficient mice failed to show the synergistic effects of IFN-gamma and MDP cotreatment on adhering and infiltrating cells.
conclusionsIFN-gamma was identified as a downstream mediator of NOD2-driven inflammation and the capacity of IFN-gamma in vivo to enhance the inflammatory potential of NOD2 was demonstrated. Extrapolation of these findings in mice suggests that the dysregulation of IFN-gamma may occur in patients with Blau syndrome, thereby contributing to the granulomatous nature of the disease.
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