ArticleProceedings of the National Academy of Sciences of the United States of America2015
CD14 dependence of TLR4 endocytosis and TRIF signaling displays ligand specificity and is dissociable in endotoxin tolerance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 140 citations in OpenAlex.
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- Quantitative Modeling of TLR Signaling Reveals Missing Negative Feedback Guiding Identification of TANK-IKKε Checkpoint.bioRxiv : the preprint server for biology · 2026Article
- Probing Immune Signatures of Conjugated Pattern Recognition Receptor Ligands Identifies Chimeras with Potent Adjuvant and Antitumor Activities.Journal of medicinal chemistry · 2026Article
- The role of immunomodulatory nano systems in the treatment of sepsis: past, present, and future.Nanomedicine (London, England) · 2026Review
- Lipopolysaccharide promotes bladder cancer immunosuppression by disrupting the Tfh/Tfr balance through TLR4 signaling.American journal of translational research · 2026Article
- Polyglutamic Acid as an Antiviral Agent: Mechanistic and Structural Insights.Pharmaceutics · 2025Review
- Porphyromonas gingivalis outer membrane vesicles divert host innate immunity and promote inflammation via C4' monophosphorylated lipid A.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- α-Tocopherol and γ-tocopherol decrease inflammatory response and insulin resistance during the interaction of adipocytes and macrophages.Nutrition research and practice · 2024Article
- Mechanism of lactic acidemia-promoted pulmonary endothelial cells death in sepsis: role for CIRP-ZBP1-PANoptosis pathway.Military Medical Research · 2024Article
- Lipid A-modified Escherichia coli can produce porcine parvovirus virus-like particles with high immunogenicity and minimal endotoxin activity.Microbial cell factories · 2024Article
- Cyclic-di-GMP induces inflammation and acute lung injury through direct binding to MD2.Clinical and translational medicine · 2024Article
- Homodimeric Granzyme A Opsonizes Mycobacterium tuberculosis and Inhibits Its Intracellular Growth in Human Monocytes via Toll-Like Receptor 4 and CD14.The Journal of infectious diseases · 2024Article
- Role of Lipopolysaccharides in the Inflammation and Pyroptosis of Alveolar Epithelial Cells in Acute Lung Injury and Acute Respiratory Distress Syndrome.Journal of inflammation research · 2024Review
- Targeting toll-like receptor 4 (TLR4) and the NLRP3 inflammasome: Novel and emerging therapeutic targets for hyperuricaemia nephropathy.Biomolecules & biomedicine · 2023Review
- A LY6E-PHB1-TRIM21 assembly degrades CD14 protein to mitigate LPS-induced inflammatory response.iScience · 2023Article
- Toll-like Receptor 4 in Acute Kidney Injury.International journal of molecular sciences · 2023Review
- Reprograming of Gene Expression of Key Inflammatory Signaling Pathways in Human Peripheral Blood Mononuclear Cells by Soybean Lectin and Resveratrol.International journal of molecular sciences · 2022Article
- TLR2 axis on peripheral blood mononuclear cells regulates inflammatory responses to non-infectious immature dengue virus particles.PLoS pathogens · 2022Article
- Externalized phosphatidylinositides on apoptotic cells are eat-me signals recognized by CD14.Cell death and differentiation · 2022Article
- Toll-like receptor-agonist-based therapies for respiratory viral diseases: thinking outside the cell.European respiratory review : an official journal of the European Respiratory Society · 2022Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Dimerization of Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) heterodimers is critical for both MyD88- and TIR-domain-containing adapter-inducing IFN-β (TRIF)-mediated signaling pathways. Recently, Zanoni et al. [(2011) Cell 147(4):868-880] reported that cluster of differentiation 14 (CD14) is required for LPS-/Escherichia coli- induced TLR4 internalization into endosomes and activation of TRIF-mediated signaling in macrophages. We confirmed their findings with LPS but report here that CD14 is not required for receptor endocytosis and downstream signaling mediated by TLR4/MD2 agonistic antibody (UT12) and synthetic small-molecule TLR4 ligands (1Z105) in murine macrophages. CD14 deficiency completely ablated the LPS-induced TBK1/IRF3 signaling axis that mediates production of IFN-β in murine macrophages without affecting MyD88-mediated signaling, including NF-κB, MAPK activation, and TNF-α and IL-6 production. However, neither the MyD88- nor TRIF-signaling pathways and their associated cytokine profiles were altered in the absence of CD14 in UT12- or 1Z105-treated murine macrophages. Eritoran (E5564), a lipid A antagonist that binds the MD2 "pocket," completely blocked LPS- and 1Z105-driven, but not UT12-induced, TLR4 dimerization and endocytosis. Furthermore, TLR4 endocytosis is induced in macrophages tolerized by exposure to either LPS or UT12 and is independent of CD14. These data indicate that TLR4 receptor endocytosis and the TRIF-signaling pathway are dissociable and that TLR4 internalization in macrophages can be induced by UT12, 1Z105, and during endotoxin tolerance in the absence of CD14.
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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.