Evidence map›Paper›PMID 33881780›Full record

ArticleThe EMBO journal2021

TPL-2 kinase induces phagosome acidification to promote macrophage killing of bacteria.

Felix Breyer, Anetta Härtlova, Teresa Thurston, Helen R Flynn, Probir Chakravarty, Julia Janzen, Julien Peltier, Tiaan Heunis, Ambrosius P Snijders, Matthias Trost and 1 more

Open access · hybridAbstract read
In one paragraph

Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

14 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Macrophages: sentinels, warriors, and healers.Human molecular genetics · 2025
    Review
  5. Article
  6. Review
  7. Article
  8. Intercalated cell function, kidney innate immunity, and urinary tract infections.Pflugers Archiv : European journal of physiology · 2024
    Review
  9. Article
  10. Assessing the Phagosome Proteome by Quantitative Mass Spectrometry.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  11. Article
  12. Article
  13. Article
  14. 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

11 authors at 3 institutions in 2 countries.

Felix BreyerThe Francis Crick Institute, London, UK.ORCID 0000-0002-9957-3209
Anetta HärtlovaBiosciences Institute, Newcastle University, Newcastle-upon-Tyne, UK.ORCID 0000-0002-8152-4361
Teresa ThurstonDepartment of Infectious Diseases, MRC Centre for Molecular Bacteriology & Infection, Imperial College London, London, UK.ORCID 0000-0001-6139-3723
Helen R FlynnThe Francis Crick Institute, London, UK.ORCID 0000-0001-7002-9130
Probir ChakravartyThe Francis Crick Institute, London, UK.ORCID 0000-0003-1146-8824
Julia JanzenThe Francis Crick Institute, London, UK.
Julien PeltierBiosciences Institute, Newcastle University, Newcastle-upon-Tyne, UK.
Tiaan HeunisBiosciences Institute, Newcastle University, Newcastle-upon-Tyne, UK.
Ambrosius P SnijdersThe Francis Crick Institute, London, UK.
Matthias TrostBiosciences Institute, Newcastle University, Newcastle-upon-Tyne, UK.ORCID 0000-0002-5732-700X
Steven C LeyThe Francis Crick Institute, London, UK.ORCID 0000-0001-5911-9223
The Francis Crick Institute · GBNewcastle University · GBImperial College London · GB

Funding

Cancer Research UKMedical Research Council MC_UP_A500_1020Medical Research Council MC_UU_12016/5Wellcome TrustWellcome Trust 215542/Z/19/Z
6 · The paper itself

Abstract

Tumour progression locus 2 (TPL-2) kinase mediates Toll-like receptor (TLR) activation of ERK1/2 and p38α MAP kinases in myeloid cells to modulate expression of key cytokines in innate immunity. This study identified a novel MAP kinase-independent regulatory function for TPL-2 in phagosome maturation, an essential process for killing of phagocytosed microbes. TPL-2 catalytic activity was demonstrated to induce phagosome acidification and proteolysis in primary mouse and human macrophages following uptake of latex beads. Quantitative proteomics revealed that blocking TPL-2 catalytic activity significantly altered the protein composition of phagosomes, particularly reducing the abundance of V-ATPase proton pump subunits. Furthermore, TPL-2 stimulated the phosphorylation of DMXL1, a regulator of V-ATPases, to induce V-ATPase assembly and phagosome acidification. Consistent with these results, TPL-2 catalytic activity was required for phagosome acidification and the efficient killing of Staphylococcus aureus and Citrobacter rodentium following phagocytic uptake by macrophages. TPL-2 therefore controls innate immune responses of macrophages to bacteria via V-ATPase induction of phagosome maturation.

Indexed as

AnimalsHumansMacrophagesMAP Kinase Kinase KinasesPhagosomesPhosphorylationProteinsSignal TransductionStaphylococcus aureusDMXL1 protein, humanMAP Kinase Kinase KinasesProteinsDMXL1macrophage phagosomeStaphylococcus aureusTPL-2 kinaseV-ATPase

Identifiers

PMID33881780
PMCPMC8126920
OpenAlexW3152853324

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.