Evidence map›Paper›PMID 15321997›Full record

ArticleInfection and immunity2004

Porphyromonas gingivalis lipopolysaccharide contains multiple lipid A species that functionally interact with both toll-like receptors 2 and 4.

Richard P Darveau, Thu-Thao T Pham, Kayde Lemley, Robert A Reife, Brian W Bainbridge, Stephen R Coats, William N Howald, Sing Sing Way, Adeline M Hajjar

Open access · greenAbstract read
In one paragraph

Article in Infection and immunity, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
237citing papers in PubMed, 3 pooled it
8.1field-weighted citation impact, top 2% 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

237 citing papers in PubMed, 3 syntheses or guidelines pooled it, 498 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
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  7. Review
  8. Article
  9. Article
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  11. Review
  12. Deciphering macrophage molecular responses toFrontiers in microbiology · 2026
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  13. Review
  14. Review
  15. Virulence · 2025
    Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Effects ofMicroorganisms · 2025
    Article

177 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

9 authors at 1 institution in 1 country.

Richard P DarveauDepartment of Periodontics, University of Washington, Health Sciences Center, Box 357444, Seattle, WA 98195, USA. rdarveau@u.washington.edu
Thu-Thao T Pham
Kayde Lemley
Robert A Reife
Brian W Bainbridge
Stephen R Coats
William N Howald
Sing Sing Way
Adeline M Hajjar
University of Washington · US

Funding

P. GINGIVALIS LPS-MODULATION OF INNATE HOST DEFENSER01DE012768 · NIDCR · UNIVERSITY OF WASHINGTON · PI DARVEAU, RICHARD PETERS · 1999 to 2014
$5.0M
ORAL BIOLOGY TRAINING SALIVARY SECRETIONST32DE007023 · NIDCR · UNIVERSITY OF WASHINGTON · PI IZUTSU, KENNETH T · 1985 to 2006
$2.3M
NIDCR NIH HHS DE12768NIDCR NIH HHS R01 DE012768NIDCR NIH HHS T32 DE007023
6 · The paper itself

Abstract

The innate host response to lipopolysaccharide (LPS) obtained from Porphyromonas gingivalis is unusual in that different studies have reported that it can be an agonist for Toll-like receptor 2 (TLR2) as well as an antagonist or agonist for TLR4. In this report it is shown that P. gingivalis LPS is highly heterogeneous, containing more lipid A species than previously described. In addition, purification of LPS can preferentially fractionate these lipid A species. It is shown that an LPS preparation enriched for lipid A species at m/z 1,435 and 1,450 activates human and mouse TLR2, TLR2 plus TLR1, and TLR4 in transiently transfected HEK 293 cells coexpressing membrane-associated CD14. The HEK cell experiments further demonstrated that cofactor MD-2 was required for functional engagement of TLR4 but not of TLR2 nor TLR2 plus TLR1. In addition, serum-soluble CD14 effectively transferred P. gingivalis LPS to TLR2 plus TLR1, but poorly to TLR4. Importantly, bone marrow cells obtained from TLR2(-/-) and TLR4(-/-) mice also responded to P. gingivalis LPS in a manor consistent with the HEK results, demonstrating that P. gingivalis LPS can utilize both TLR2 and TLR4. No response was observed from bone marrow cells obtained from TLR2 and TLR4 double-knockout mice, demonstrating that P. gingivalis LPS activation occurred exclusively through either TLR2 or TLR4. Although the biological significance of the different lipid A species found in P. gingivalis LPS preparations is not currently understood, it is proposed that the presence of multiple lipid A species contributes to cell activation through both TLR2 and TLR4.

Indexed as

AnimalsBone Marrow CellsCell LineHumansLipid ALipopolysaccharidesMembrane GlycoproteinsMiceMice, Inbred C57BLMice, KnockoutPorphyromonas gingivalisReceptors, Cell SurfaceToll-Like Receptor 1Toll-Like Receptor 2Toll-Like Receptor 4Toll-Like ReceptorsLipid ALipopolysaccharidesMembrane GlycoproteinsReceptors, Cell SurfaceTLR2 protein, humanTLR4 protein, humanToll-Like Receptor 1Toll-Like Receptor 2Toll-Like Receptor 4Toll-Like Receptors

Identifiers

PMID15321997
PMCPMC517442
OpenAlexW2107715779

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.