ArticleScience signaling2014
Type I interferon signaling contributes to the bias that Toll-like receptor 4 exhibits for signaling mediated by the adaptor protein TRIF.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
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- Mechanisms of immune regulation by the placenta: Role of type I interferon and interferon-stimulated genes signaling during pregnancy.Immunological reviews · 2022Review
- RING finger protein TOPORS modulates the expression of tumor suppressor SMAR1 in colorectal cancer via the TLR4-TRIF pathway.Molecular oncology · 2022Article
- Type I Interferon-Mediated Regulation of Antiviral Capabilities of Neutrophils.International journal of molecular sciences · 2021Review
- Microbial Lipid A Remodeling Controls Cross-Presentation Efficiency and CD8 T Cell Priming by Modulating Dendritic Cell Function.Infection and immunity · 2021Article
- Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function.Journal of leukocyte biology · 2020Article
- Dissociation of TRIF bias and adjuvanticity.Vaccine · 2020Article
- Type I IFN, Ly6CMolecular cancer therapeutics · 2020Article
- Surface Immunogenic Protein ofVaccines · 2020Article
- House dust mite exposure attenuates influenza A infection in a mouse model of pulmonary allergic inflammation.Microbial pathogenesis · 2019Article
- Relevance of placental type I interferon beta regulation for pregnancy success.Cellular & molecular immunology · 2018Article
- Kudzu Leaf Extract Suppresses the Production of Inducible Nitric Oxide Synthase, Cyclooxygenase-2, Tumor Necrosis Factor-Alpha, and Interleukin-6 via Inhibition of JNK, TBK1 and STAT1 in Inflammatory Macrophages.International journal of molecular sciences · 2018Article
- Diverse pro-inflammatory endotoxin recognition systems of mammalian innate immunity.F1000Research · 2018Review
- Versican is produced by Trif- and type I interferon-dependent signaling in macrophages and contributes to fine control of innate immunity in lungs.American journal of physiology. Lung cellular and molecular physiology · 2017Article
- Newborn susceptibility to infection vs. disease depends on complex in vivo interactions of host and pathogen.Seminars in immunopathology · 2017Review
- IL-8 and IP-10 expression from human bronchial epithelial cells BEAS-2B are promoted by Streptococcus pneumoniae endopeptidase O (PepO).BMC microbiology · 2017Article
- S100-alarmin-induced innate immune programming protects newborn infants from sepsis.Nature immunology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Signaling by Toll-like receptor 4 (TLR4) is mediated by either of two adaptor proteins: myeloid differentiation marker 88 (MyD88) or Toll-interleukin-1 (IL-1) receptor (TIR) domain-containing adaptor inducing interferon-β (TRIF). Whereas MyD88-mediated signaling leads to proinflammatory responses, TRIF-mediated signaling leads to less toxic immunostimulatory responses that are beneficial in boosting vaccine responses. The hypothesis that monophosphorylated lipid A structures act as TRIF-biased agonists of TLR4 offered a potential mechanism to explain their clinical value as vaccine adjuvants, but studies of TRIF-biased agonists have been contradictory. In experiments with mouse dendritic cells, we found that irrespective of the agonist used, TLR4 functioned as a TRIF-biased signaling system through a mechanism that depended on the autocrine and paracrine effects of type I interferons. The TLR4 agonist synthetic lipid A induced expression of TRIF-dependent genes at lower concentrations than were necessary to induce the expression of genes that depend on MyD88-mediated signaling. Blockade of type I interferon signaling selectively decreased the potency of lipid A (increased the concentration required) in inducing the expression of TRIF-dependent genes, thereby eliminating adaptor bias. These data may explain how high-potency TLR4 agonists can act as clinically useful vaccine adjuvants by selectively activating TRIF-dependent signaling events required for immunostimulation, without or only weakly activating potentially harmful MyD88-dependent inflammatory responses.
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