ArticleInfection and immunity2009
Francisella tularensis induces ubiquitin-dependent major histocompatibility complex class II degradation in activated macrophages.
Article in Infection and immunity, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 43 citations in OpenAlex.
- The subset of M1-paired MHC class II conformers is critical for CD4+ T cell activation.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Review
- Proximity-Based Labeling Identifies MHC Class II and CD37 as B Cell Receptor-Proximal Proteins with Immunological Functions.ImmunoHorizons · 2024Article
- The Ubiquitination System within Bacterial Host-Pathogen Interactions.Microorganisms · 2021Review
- Targeting the ubiquitination/deubiquitination process to regulate immune checkpoint pathways.Signal transduction and targeted therapy · 2021Review
- Murine macrophage TLR2-FcγR synergy via FcγR licensing of IL-6 cytokine mRNA ribosome binding and translation.PloS one · 2018Article
- Giving CD4+ T cells the slip: viral interference with MHC class II-restricted antigen processing and presentation.Current opinion in immunology · 2016Review
- Francisella tularensis Catalase Restricts Immune Function by Impairing TRPM2 Channel Activity.The Journal of biological chemistry · 2016Article
- The ins and outs of MHC class II-mediated antigen processing and presentation.Nature reviews. Immunology · 2015Review
- Francisella tularensis LVS induction of prostaglandin biosynthesis by infected macrophages requires specific host phospholipases and lipid phosphatases.Infection and immunity · 2014Article
- A dose and time response Markov model for the in-host dynamics of infection with intracellular bacteria following inhalation: with application to Francisella tularensis.Journal of the Royal Society, Interface · 2014Article
- Janus kinase 3 activity is necessary for phosphorylation of cytosolic phospholipase A2 and prostaglandin E2 synthesis by macrophages infected with Francisella tularensis live vaccine strain.Infection and immunity · 2014Article
- A Francisella virulence factor catalyses an essential reaction of biotin synthesis.Molecular microbiology · 2014Article
- Uncovering the components of the Francisella tularensis virulence stealth strategy.Frontiers in cellular and infection microbiology · 2014Review
- Host-pathogen interactions and immune evasion strategies in Francisella tularensis pathogenicity.Infection and drug resistance · 2014Review
- MHC class II antigen presentation by dendritic cells regulated through endosomal sorting.Cold Spring Harbor perspectives in biology · 2013Review
- Regulation of MHC Class II-Peptide Complex Expression by Ubiquitination.Frontiers in immunology · 2013Review
- FcγR-driven release of IL-6 by macrophages requires NOX2-dependent production of reactive oxygen species.The Journal of biological chemistry · 2013Article
- Temporal transcriptional response during infection of type II alveolar epithelial cells with Francisella tularensis live vaccine strain (LVS) supports a general host suppression and bacterial uptake by macropinocytosis.The Journal of biological chemistry · 2013Article
- Presentation of phagocytosed antigens by MHC class I and II.Traffic (Copenhagen, Denmark) · 2013Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The intracellular bacterium Francisella tularensis survives and replicates within macrophages, ultimately killing the host cell. Resolution of infection requires the development of adaptive immunity through presentation of F. tularensis antigens to CD4+ and CD8+ T cells. We have previously established that F. tularensis induces macrophage prostaglandin E2 (PGE2) production, leading to skewed T-cell responses. PGE2 can also downregulate macrophage major histocompatibility complex (MHC) class II expression, suggesting that F. tularensis-elicited PGE2 may further alter T-cell responses via inhibition of class II expression. To test this hypothesis, gamma interferon (IFN-gamma)-activated reporter macrophages were exposed to supernatants from F. tularensis-infected macrophages, and the class II levels were measured. Exposure of macrophages to infection supernatants results in essentially complete clearance of surface class II and CD86, compromising the macrophage's ability to present antigens to CD4 T cells. Biochemical analysis revealed that infection supernatants elicit ubiquitin-dependent class II downregulation and degradation within intracellular acidic compartments. By comparison, exposure to PGE2 alone only leads to a minor decrease in macrophage class II expression, demonstrating that a factor distinct from PGE2 is eliciting the majority of class II degradation. However, production of this non-PGE2 factor is dependent on macrophage cyclooxygenase activity and is induced by PGE2. These results establish that F. tularensis induces the production of a PGE2-dependent factor that elicits MHC class II downregulation in IFN-gamma-activated macrophages through ubiquitin-mediated delivery of class II to lysosomes, establishing another mechanism for the modulation of macrophage antigen presentation during F. tularensis infection.
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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.