ReviewCellular and molecular life sciences : CMLS2021
TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling.
Review in Cellular and molecular life sciences : CMLS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 785 papers, 2 of them syntheses that pooled it.
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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
785 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,313 citations in OpenAlex.
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- Social disconnection integrates genetic and proteomic risks in suicidal ideation and depression.Translational psychiatry · 2026Article
- From metabolites to membrane vesicles: Unifying gut microbial signals in obesity, t2dm, and MASLD.World journal of microbiology & biotechnology · 2026Review
- The Gut Microbiome as a Mechanistic Link Between the Planetary Health Diet and Healthy Aging.Nutrients · 2026Review
- CSA-13 treatment in a murine model of Pseudomonas pneumonia-induced sepsis and its effects on renal injury, inflammation, and glycocalyx derangement.The Journal of antibiotics · 2026Article
- Immune dysregulation and gut microbiota: Connection to health and disease development.Neural regeneration research · 2026Article
- Targeting the human gut microbiome: a comparative review of probiotics, prebiotics, synbiotics, and postbiotics.Journal of advanced research · 2026Review
- The endothelin-1/TLR4/NF-κB/NLRP3 inflammasome axis in preeclampsia: a review of a pathological feed-forward loop and therapeutic frontier.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Heat stress enhances gut microbial arginine catabolism to amplify MyD88-dependent inflammatory responses.Microbiome · 2026Article
- Immunization with the Tc85-Derived Peptide Displayed on Virus-like Particles Confers Protection againstACS omega · 2026Article
- Uncoupling Type I Interferon Benefits From Inflammatory Toxicity: Transformer-Prioritized Precision Agonists for Potent and Safer Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genome-Guided Probiotic Mechanisms of Enterococcus hirae SMU2502: Wnt/β-catenin-Driven Intestinal Epithelial Proliferation and Protection Against Salmonella Infection.Probiotics and antimicrobial proteins · 2026Article
- Quantitative Modeling of TLR Signaling Reveals Missing Negative Feedback Guiding Identification of TANK-IKKε Checkpoint.bioRxiv : the preprint server for biology · 2026Article
725 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Toll-like receptor (TLR) 4 belongs to the TLR family of receptors inducing pro-inflammatory responses to invading pathogens. TLR4 is activated by lipopolysaccharide (LPS, endotoxin) of Gram-negative bacteria and sequentially triggers two signaling cascades: the first one involving TIRAP and MyD88 adaptor proteins is induced in the plasma membrane, whereas the second engaging adaptor proteins TRAM and TRIF begins in early endosomes after endocytosis of the receptor. The LPS-induced internalization of TLR4 and hence also the activation of the TRIF-dependent pathway is governed by a GPI-anchored protein, CD14. The endocytosis of TLR4 terminates the MyD88-dependent signaling, while the following endosome maturation and lysosomal degradation of TLR4 determine the duration and magnitude of the TRIF-dependent one. Alternatively, TLR4 may return to the plasma membrane, which process is still poorly understood. Therefore, the course of the LPS-induced pro-inflammatory responses depends strictly on the rates of TLR4 endocytosis and trafficking through the endo-lysosomal compartment. Notably, prolonged activation of TLR4 is linked with several hereditary human diseases, neurodegeneration and also with autoimmune diseases and cancer. Recent studies have provided ample data on the role of diverse proteins regulating the functions of early, late, and recycling endosomes in the TLR4-induced inflammation caused by LPS or phagocytosis of E. coli. In this review, we focus on the mechanisms of the internalization and intracellular trafficking of TLR4 and CD14, and also of LPS, in immune cells and discuss how dysregulation of the endo-lysosomal compartment contributes to the development of diverse human diseases.
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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.