ArticleScience advances2021
TRAF6-IRF5 kinetics, TRIF, and biophysical factors drive synergistic innate responses to particle-mediated MPLA-CpG co-presentation.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
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- Robust Bioconjugated Antigens Induce Immune Responses Preventing Malaria Infection and its Transmission.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Rational design of immunogenic nanoparticles as a platform to reduce ovarian tumor burden in mice.International journal of pharmaceutics · 2025Article
- Super-adjuvant nanoparticles for platform cancer vaccination.Cell reports. Medicine · 2025Article
- Optogenetic-Controlled iPSC-Based Vaccines for Prophylactic and Therapeutic Tumor Suppression in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A Dual-Adjuvanted Parenteral-Intranasal Subunit Nanovaccine generates Robust Systemic and Mucosal Immunity Against SARS-CoV-2 in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- Nanocarrier design for pathogen-inspired innate immune agonist delivery.Trends in immunology · 2024Review
- A Cancer Nanovaccine for Co-Delivery of Peptide Neoantigens and Optimized Combinations of STING and TLR4 Agonists.ACS nano · 2024Article
- Engineering approaches for innate immune-mediated tumor microenvironment remodeling.Immuno-oncology technology · 2024Review
- Single-cell epitope-transcriptomics reveal lung stromal and immune cell response kinetics to nanoparticle-delivered RIG-I and TLR4 agonists.Biomaterials · 2023Article
- Roles of Mitochondrial DNA Damage in Kidney Diseases: A New Biomarker.International journal of molecular sciences · 2022Review
- Bioinspired vaccines to enhance MHC class-I antigen cross-presentation.Current opinion in immunology · 2022Review
- Nanoparticle-delivered TLR4 and RIG-I agonists enhance immune response to SARS-CoV-2 subunit vaccine.Journal of controlled release : official journal of the Controlled Release Society · 2022Article
- Cytokine Responses to Adenovirus and Adenovirus Vectors.Viruses · 2022Review
- Homotypic targeting of immunomodulatory nanoparticles for enhanced peripheral and central immunity.Cell proliferation · 2022Article
- Dual agonist immunostimulatory nanoparticles combine with PD1 blockade for curative neoadjuvant immunotherapy of aggressive cancers.Nanoscale · 2022Article
- MicroRNA 322-5p reduced neuronal inflammation via the TLR4/TRAF6/NF-κB axis in a rat epilepsy model.Open medicine (Warsaw, Poland) · 2022Article
- Chlorogenic Acid Alleviates the Inflammatory Stress of LPS-Induced BV2 Cell via Interacting with TLR4-Mediated Downstream Pathway.Computational and mathematical methods in medicine · 2022Article
- Soluble and Microparticle-Based Delivery of TLR4 and TLR9 Agonists Differentially Modulate 3D Chemotaxis of Bone Marrow-Derived Dendritic Cells.Advanced healthcare materials · 2021Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Innate immune responses to pathogens are driven by co-presentation of multiple pathogen-associated molecular patterns (PAMPs). Combinations of PAMPs can trigger synergistic immune responses, but the underlying molecular mechanisms of synergy are poorly understood. Here, we used synthetic particulate carriers co-loaded with monophosphoryl lipid A (MPLA) and CpG as pathogen-like particles (PLPs) to dissect the signaling pathways responsible for dual adjuvant immune responses. PLP-based co-delivery of MPLA and CpG to GM-CSF-driven mouse bone marrow-derived antigen-presenting cells (BM-APCs) elicited synergistic interferon-β (IFN-β) and interleukin-12p70 (IL-12p70) responses, which were strongly influenced by the biophysical properties of PLPs. Mechanistically, we found that MyD88 and interferon regulatory factor 5 (IRF5) were necessary for IFN-β and IL-12p70 production, while TRIF signaling was required for the synergistic response. Both the kinetics and magnitude of downstream TRAF6 and IRF5 signaling drove the synergy. These results identify the key mechanisms of synergistic Toll-like receptor 4 (TLR4)-TLR9 co-signaling in mouse BM-APCs and underscore the critical role of signaling kinetics and biophysical properties on the integrated response to combination adjuvants.
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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.