ArticleJournal of immunology (Baltimore, Md. : 1950)2009
Direct stimulation of tlr5+/+ CD11c+ cells is necessary for the adjuvant activity of flagellin.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 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
46 citing papers in PubMed, 85 citations in OpenAlex.
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- Am80-lipid nanoparticles serve as an enteric mucosal adjuvant following parenteral immunization with inactivated polio vaccine.Science advances · 2026Article
- Co-Delivery of Multiple Toll-Like Receptor Agonists and Avian Influenza Hemagglutinin on Protein Nanoparticles Enhances Vaccine Immunogenicity and Efficacy.Advanced healthcare materials · 2025Article
- Intestinal flora plays a role in the progression of hepatitis-cirrhosis-liver cancer.Frontiers in cellular and infection microbiology · 2023Review
- Nasal immunization with H7 flagellin protects mice against hemolytic uremic syndrome secondary toFrontiers in cellular and infection microbiology · 2023Article
- Naïve CD4International journal of molecular sciences · 2022Article
- Immunogenic Modification of Ligilactobacillus agilis by Specific Amino Acid Substitution of Flagellin.Applied and environmental microbiology · 2022Article
- FliC's Hypervariable D3 Domain Is Required for Robust Anti-Flagellin Primary Antibody Responses.ImmunoHorizons · 2019Article
- Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines.Pharmaceutics · 2019Article
- A Fusion Protein of Derp2 Allergen and Flagellin Suppresses Experimental Allergic Asthma.Allergy, asthma & immunology research · 2019Article
- Chemical and Immunological Characteristics of Aluminum-Based, Oil-Water Emulsion, and Bacterial-Origin Adjuvants.Journal of immunology research · 2019Review
- An R848 adjuvanted influenza vaccine promotes early activation of B cells in the draining lymph nodes of non-human primate neonates.Immunology · 2018Article
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- Activation of NLRC4 downregulates TLR5-mediated antibody immune responses against flagellin.Cellular & molecular immunology · 2016Article
- Flagellin Modulates the Function of Invariant NKT Cells From Patients With Asthma via Dendritic Cells.Allergy, asthma & immunology research · 2016Article
- Carboxyl-terminal fusion of E7 into Flagellin shifts TLR5 activation to NLRC4/NAIP5 activation and induces TLR5-independent anti-tumor immunity.Scientific reports · 2016Article
- Investigations of Enantiopure Nicotine Haptens Using an Adjuvanting Carrier in Anti-Nicotine Vaccine Development.Journal of medicinal chemistry · 2016Article
- Utilizing a TLR5-Adjuvanted Cytomegalovirus as a Lentiviral Vaccine in the Nonhuman Primate Model for AIDS.PloS one · 2016Article
- Flagellin Encoded in Gene-Based Vector Vaccines Is a Route-Dependent Immune Adjuvant.PloS one · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Flagellin is a highly effective adjuvant, but the cellular mechanism underlying this activity remains uncertain. More specifically, no consensus exists as to whether flagellin activates dendritic cells (DC) directly or indirectly. Intramuscular immunization with flagellin-OVA fusion protein resulted in enhanced in vivo T cell clustering in draining lymph nodes and IL-2 production by OVA-specific CD4(+) T cells. Immunization with flagellin-OVA also triggered greater levels of Ag-specific CD4(+) T cell proliferation than immunization with flagellin and OVA as separate proteins. To determine whether flagellin, in the context of a fusion protein with OVA, was acting directly on DC, we used a combination of CD4(+) T cell adoptive transfers and bone marrow chimera mice in which the presence or absence of potential tlr5(+/+) CD11c(+) cells was controlled by injection of diphtheria toxin. The Ag-specific CD4(+) T cell response in mice with CD11c(+) cells from a tlr5(-/-) background and mixed populations of all other hematopoietic cells was dramatically reduced in comparison to mice that had DC from tlr5(-/-) and wild-type backgrounds. Immunization of MyD88(-/-)tlr5(+/+) mice revealed that the enhanced response following immunization with flagellin-OVA is dependent on signaling via the TLR5-MyD88 pathway as well as enhanced Ag uptake and processing resulting from Ag targeting via TLR5. In summary, our data are consistent with the conclusion that direct stimulation of tlr5(+/+) CD11c(+) cells is necessary for the adjuvant activity of a flagellin fusion protein and that this adjuvant effect requires signaling through TLR5.
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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.