Evidence map›Paper›PMID 18490457›Full record

ArticleInfection and immunity2008

Differential activation of human and mouse Toll-like receptor 4 by the adjuvant candidate LpxL1 of Neisseria meningitidis.

Liana Steeghs, A Marijke Keestra, Andries van Mourik, Heli Uronen-Hansson, Peter van der Ley, Robin Callard, Nigel Klein, Jos P M van Putten

Open access · greenAbstract read
In one paragraph

Article in Infection and immunity, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

43 citing papers in PubMed, 74 citations in OpenAlex.

  1. Trial
  2. Review
  3. mBio · 2023
    Article
  4. bioRxiv : the preprint server for biology · 2023
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  5. Article
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  7. Review
  8. Article
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  15. [Composition and mode of action of adjuvants in licensed viral vaccines].Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz · 2019
    Review
  16. Article
  17. Frontiers in immunology · 2018
    Article
  18. Review
  19. Review
  20. Article
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

8 authors at 2 institutions in 2 countries.

Liana SteeghsDepartment of Infectious Diseases and Immunology, University of Utrecht, Yalelaan 1, 3584 CL Utrecht, The Netherlands. l.steeghs@uu.nl
A Marijke Keestra
Andries van Mourik
Heli Uronen-Hansson
Peter van der Ley
Robin Callard
Nigel Klein
Jos P M van Putten
Utrecht University · NLUniversity College London · GB

Funding

Biotechnology and Biological Sciences Research CouncilMedical Research Council
6 · The paper itself

Abstract

Neisseria meningitidis LpxL1 lipopolysaccharide (LPS) bearing penta-acylated lipid A is considered a promising adjuvant candidate for inclusion in future N. meningitidis vaccines, as it elicits a markedly reduced endotoxic response in human macrophages relative to that in wild-type (hexa-acylated) LPS, while it is an equally effective adjuvant in mice. As dendritic cells (DC) and Toll-like receptors (TLR) are regarded as central mediators in the initiation of an immune response, here we evaluated the ability of LpxL1 LPS to mature and to activate human DC and examined its TLR4-/MD-2-activating properties. Unexpectedly, purified LpxL1 LPS displayed minimal human DC-stimulating properties compared to wild-type LPS. Although whole bacteria induced DC maturation and activation irrespective of their type of LPS, the LpxL1 mutant failed to activate the human recombinant TLR4/MD-2 complex expressed in HeLa cells. Similarly, purified LpxL1 LPS was unable to activate human TLR4/MD-2 and it even acted as an antagonist of wild-type LPS. Both wild-type and LpxL1 LPSs activated the murine TLR4/MD-2 complex, consistent with their abilities to induce maturation and activation of murine DC. Assays with cells transfected with different combinations of human and murine TLR4 and MD-2 indicated that TLR4 was a more-major determinant of the LPS response than MD-2. The species-specific activation of the TLR4/MD-2 complex by LpxL1 LPS may have an impact on the use of LpxL1 LPS as an adjuvant and the use of murine immunization models in human meningococcal vaccine development.

Indexed as

AnimalsDendritic CellsHeLa CellsHumansLipid ALymphocyte Antigen 96MiceNeisseria meningitidisToll-Like Receptor 4Lipid ALY96 protein, humanLy96 protein, mouseLymphocyte Antigen 96TLR4 protein, humanTlr4 protein, mouseToll-Like Receptor 4

Identifiers

PMID18490457
PMCPMC2493235
OpenAlexW1997895282

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.