CoChat
Sign Up
Cited by 65Immune Response and InflammationInflammasome and immune disordersEscherichia coli research studies

Antagonistic lipopolysaccharides block E. coli lipopolysaccharide function at human TLR4 via interaction with the human MD-2 lipopolysaccharide binding site: Antagonistic LPSs bind to hMD-2

Coats, Stephen R., Do, Christopher T., Karimi-Naser, Lisa M., Braham, Pamela H., Darveau, Richard P.·2007·Cellular Microbiology
DOI 10.1111/j.1462-5822.2006.00859.x
Open this paper in CoChat — free account

Abstract

Lipopolysaccharides containing underacylated lipid A structures exhibit reduced abilities to activate the human (h) Toll-like receptor 4 (TLR4) signalling pathway and function as potent antagonists against lipopolysaccharides bearing canonical lipid A structures. Expression of underacylated lipopolysaccharides has emerged as a novel mechanism utilized by microbial pathogens to modulate host innate immune responses. Notably, antagonistic lipopolysaccharides are prime therapeutic candidates for combating Gram negative bacterial sepsis. Penta-acylated msbB and tetra-acylated Porphyromonas gingivalis lipopolysaccharides functionally antagonize hexa-acylated Escherichia coli lipopolysaccharide-dependent activation of hTLR4 through the coreceptor, hMD-2. Here, the molecular mechanism by which these antagonistic lipopolysaccharides act at hMD-2 is examined. We present evidence that both msbB and P. gingivalis lipopolysaccharides are capable of direct binding to hMD-2. These antagonistic lipopolysaccharides can utilize at least two distinct mechanisms to block E. coli lipopolysaccharide-dependent activation of hTLR4. The main mechanism consists of direct competition between the antagonistic lipopolysaccharides and E. coli lipopolysaccharide for the same binding site on hMD-2, while the secondary mechanism involves the ability of antagonistic lipopolysaccharide-hMD-2 complexes to inhibit E. coli lipopolysaccharide-hMD-2 complexes function at hTLR4. It is also shown that both hTLR4 and hMD-2 contribute to the species-specific recognition of msbB and P. gingivalis lipopolysaccharides as antagonists at the hTLR4 complex.

Integrity signals

Registry

Crossref · 10.1111/j.1462-5822.2006.00859.x

Cites

59 of 59 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Hexa-acylated LPS potently activates human TLR4/MD2, whereas hypo-acylated tetra- and penta-acylated LPS poorly activate or antagonize human TLR4/MD2 activation driven by hexa-acylated LPS.

    “it has been previously shown that hexa-acylated LPS potently activates human TLR4/MD2, whereas hypo-acylated tetra- and penta-acylated LPS poorly activate or antagonize human TLR4/MD2 activation driven by hexa-acylated LPS22,23.”

    From Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses (2025) · cites this paper as [22]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Coats, S. R., Do, C. T., Karimi-Naser, L. M., Braham, P. H., & Darveau, R. P.
Affiliations
University of Washington (US)
ORCID
Darveau, Richard P.
Venue
Cellular Microbiology
Publisher
Hindawi Limited
Published
2006-12-06
Volume
9
Issue
5
Pages
1191-1202
ISSN
1462-5814 (ISSN-L)
DOI
10.1111/j.1462-5822.2006.00859.x
OpenAlex
W1982498329
Cited by
65
References
59
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 2 · 2014: 8 · 2013: 2 · 2012: 2
FWCI
1.77
Type
journal article
Language
en
Open access
closed
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 3191 d)
Locations
  • Cellular Microbiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Dental and Craniofacial Research (DE12768, R01DE013325, DE13325, R01DE012768)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
Keywords
TLR4, MD-2, lipid A acylation, Porphyromonas gingivalis, Escherichia coli lipopolysaccharide, gram-negative sepsis, innate immune modulation, species-specific recognition, TLR4 signaling
MeSH terms
Animals, Binding Sites, Cell Line, Escherichia coli, Humans, Lipid A, Lipopolysaccharides, Protein Binding, Signal Transduction, Porphyromonas gingivalis, Biotinylation, Immunoprecipitation, Toll-Like Receptor 4, Lymphocyte Antigen 96, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review