Evidence map›Paper›PMID 28826648›Full record

ArticleCytokine2017

The synergistic effects of combining TLR ligand based adjuvants on the cytokine response are dependent upon p38/JNK signalling.

Lucia Fischetti, Ziyun Zhong, Christopher L Pinder, John S Tregoning, Robin J Shattock

Open access · hybridAbstract read
In one paragraph

Article in Cytokine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

27 citing papers in PubMed, 37 citations in OpenAlex.

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  9. Thrombocytopenia in Sepsis.Life (Basel, Switzerland) · 2025
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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

5 authors at 1 institution in 1 country.

Lucia FischettiMucosal Infection & Immunity Group, Section of Virology, Imperial College London, St. Mary's Campus, London W2 1PG, United Kingdom.
Ziyun ZhongMucosal Infection & Immunity Group, Section of Virology, Imperial College London, St. Mary's Campus, London W2 1PG, United Kingdom.
Christopher L PinderMucosal Infection & Immunity Group, Section of Virology, Imperial College London, St. Mary's Campus, London W2 1PG, United Kingdom.
John S TregoningMucosal Infection & Immunity Group, Section of Virology, Imperial College London, St. Mary's Campus, London W2 1PG, United Kingdom.
Robin J ShattockMucosal Infection & Immunity Group, Section of Virology, Imperial College London, St. Mary's Campus, London W2 1PG, United Kingdom. Electronic address: r.shattock@imperial.ac.uk.
Imperial College London · GB

Funding

Viral Sequencing CoreU19AI067854 · NIAID · DUKE UNIVERSITY · PI CRUMP, JOHN ANDREW · 2006 to 2011
$290.5M
NIAID NIH HHS U19 AI067854
6 · The paper itself

Abstract

Toll like receptor (TLR) ligands are important adjuvant candidates, causing antigen presenting cells to release inflammatory mediators, leading to the recruitment and activation of other leukocytes. The aim of this study was to define the response of human blood derived dendritic cells and macrophages to three TLR ligands acting singly or in combination, Poly I:C (TLR3), GLA (TLR4) and R848 (TLR7/8). Combinations of TLR agonists have been shown to have a synergistic effect on individual cytokines, here we look at the global inflammatory response measuring both cytokines and chemokines. Using a custom Luminex assay we saw dose responses in several mediators including CCL3 (MIP1α), IL-1α, IL-1β, IL-12, CXCL10 (IP-10) and IL-6, all of which were significantly increased by the combination of R848 and GLA, even when low dose GLA was added. The synergistic effect was inhibited by specific MAP kinase inhibitors blocking the kinases p38 and JNK but not MEK1. Combining TLR adjuvants also had a synergistic effect on cytokine responses in human mucosal tissue explants. From this we conclude that the combination of R848 and GLA potentiates the inflammatory profile of antigen presenting cells. Since the pattern of inflammatory mediators released can alter the quality and quantity of the adaptive immune response to vaccination, this study informs vaccine adjuvant design.

Indexed as

MAP Kinase Signaling SystemAdjuvants, PharmaceuticBiomarkersChemokinesCytokinesDendritic CellsHumansImidazolesInflammation MediatorsJNK Mitogen-Activated Protein KinasesLigandsMacrophagesMitogen-Activated Protein Kinase KinasesMyeloid Differentiation Factor 88p38 Mitogen-Activated Protein KinasesToll-Like ReceptorsAdjuvants, PharmaceuticBiomarkersChemokinesCytokinesImidazolesInflammation MediatorsJNK Mitogen-Activated Protein KinasesLigandsMitogen-Activated Protein Kinase KinasesMyeloid Differentiation Factor 88p38 Mitogen-Activated Protein KinasesresiquimodToll-Like ReceptorsAdjuvantCytokineMucosalSynergyTLR

Identifiers

PMID28826648
PMCPMC6169299
OpenAlexW2745643930

What OpenQuestion holds

Textmetadata
LicenceTDM
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.