Evidence map›Paper›PMID 23430250›Full record

ArticleThe Journal of biological chemistry2013

Human lipopolysaccharide-binding protein (LBP) and CD14 independently deliver triacylated lipoproteins to Toll-like receptor 1 (TLR1) and TLR2 and enhance formation of the ternary signaling complex.

Diana Rose E Ranoa, Stacy L Kelley, Richard I Tapping

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

69 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Review
  5. Article
  6. Article
  7. Enhancing CAR T-Cell Function with Domains of Innate Immunity Sensors.International journal of molecular sciences · 2025
    Review
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  14. Review
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  16. Review
  17. Atheroma-Relevant 7-Oxysterols Differentially Upregulate Cd14 Expression.International journal of molecular sciences · 2023
    Article
  18. Article
  19. Article
  20. Heightened Microbial Translocation Is a Prognostic Biomarker of Recurrent Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
    Article

9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Diana Rose E RanoaDepartment of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.
Stacy L KelleyDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.
Richard I TappingDepartment of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; Department of College of Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801. Electronic address: tapping@illinois.edu.
University of Illinois Urbana-Champaign · US

Funding

Initiation of Toll-like Receptor SignalingR01AI052344 · NIAID · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI TAPPING, RICHARD IAN · 2005 to 2009
$1.4M
NIAID NIH HHS R01 AI052344
6 · The paper itself

Abstract

Bacterial lipoproteins are the most potent microbial agonists for the Toll-like receptor 2 (TLR2) subfamily, and this pattern recognition event induces cellular activation, leading to host immune responses. Triacylated bacterial lipoproteins coordinately bind TLR1 and TLR2, resulting in a stable ternary complex that drives intracellular signaling. The sensitivity of TLR-expressing cells to lipoproteins is greatly enhanced by two lipid-binding serum proteins known as lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14); however, the physical mechanism that underlies this increased sensitivity is not known. To address this, we measured the ability of LBP and sCD14 to drive ternary complex formation between soluble extracellular domains of TLR1 and TLR2 and a synthetic triacylated lipopeptide agonist. Importantly, addition of substoichiometric amounts of either LBP or sCD14 significantly enhanced formation of a TLR1·TLR2 lipopeptide ternary complex as measured by size exclusion chromatography. However, neither LBP nor sCD14 was physically associated with the final ternary complex. Similar results were obtained using outer surface protein A (OspA), a naturally occurring triacylated lipoprotein agonist from Borrelia burgdorferi. Activation studies revealed that either LBP or sCD14 sensitized TLR-expressing cells to nanogram levels of either the synthetic lipopeptide or OspA lipoprotein agonist. Together, our results show that either LBP or sCD14 can drive ternary complex formation and TLR activation by acting as mobile carriers of triacylated lipopeptides or lipoproteins.

Indexed as

Acute-Phase ProteinsBacteremiaBacterial ProteinsBinding, CompetitiveCarrier ProteinsEnzyme-Linked Immunosorbent AssayHEK293 CellsHumansImmunity, InnateInflammationLipopeptidesLipopolysaccharide-Binding ProteinLipopolysaccharide ReceptorsMembrane GlycoproteinsProtein BindingRecombinant ProteinsAcute-Phase ProteinsBacterial ProteinsCarrier ProteinsLipopeptidesLipopolysaccharide-Binding ProteinLipopolysaccharide ReceptorsMembrane GlycoproteinsRecombinant ProteinsToll-Like Receptor 1Toll-Like Receptor 2

Identifiers

PMID23430250
PMCPMC3617275
OpenAlexW2090854355

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.