Evidence map›Paper›PMID 24638169›Full record

ArticleThe Journal of experimental medicine2014

Oxidative metabolism enables Salmonella evasion of the NLRP3 inflammasome.

Meghan A Wynosky-Dolfi, Annelise G Snyder, Naomi H Philip, Patrick J Doonan, Maya C Poffenberger, Daina Avizonis, Erin E Zwack, Amber M Riblett, Baofeng Hu, Till Strowig and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
6.1field-weighted citation impact, top 3% 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

58 citing papers in PubMed, 103 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Journal of inflammation research · 2025
    Review
  7. Article
  8. Review
  9. Review
  10. NLRP3 Inflammasomes: Dual Function in Infectious Diseases.Journal of immunology (Baltimore, Md. : 1950) · 2024
    Review
  11. Infection and immunity · 2024
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Microorganisms · 2022
    Article
  20. Review
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

14 authors at 6 institutions in 4 countries.

Meghan A Wynosky-DolfiDepartment of Pathobiology, School of Veterinary Medicine; and 2 Immunology Graduate Group and 3 Cell and Molecular Biology Graduate Group, University of Pennsylvania, Kennett Square, PA 19104.
Annelise G Snyder
Naomi H Philip
Patrick J Doonan
Maya C Poffenberger
Daina Avizonis
Erin E Zwack
Amber M Riblett
Baofeng Hu
Till Strowig
Richard A Flavell
Russell G Jones
Bruce D Freedman
Igor E Brodsky
University of Pennsylvania · USGoodman (Japan) · JPHoward Hughes Medical Institute · USMcGill University · CAOccupational Cancer Research Centre · CAYale University · US

Funding

TRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Ken Hashigiwa Cadwell · 1997 to 2026
$32.5M
Mechanisms of Inflammasome Inhibition by SalmonellaR21AI105346 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI BRODSKY, IGOR E · 2013 to 2014
$440k
NIAID NIH HHS AI105346NIAID NIH HHS R21 AI105346NIDDK NIH HHS P30 DK050306NIDDK NIH HHS P30-DK050306
6 · The paper itself

Abstract

Microbial infection triggers assembly of inflammasome complexes that promote caspase-1-dependent antimicrobial responses. Inflammasome assembly is mediated by members of the nucleotide binding domain leucine-rich repeat (NLR) protein family that respond to cytosolic bacterial products or disruption of cellular processes. Flagellin injected into host cells by invading Salmonella induces inflammasome activation through NLRC4, whereas NLRP3 is required for inflammasome activation in response to multiple stimuli, including microbial infection, tissue damage, and metabolic dysregulation, through mechanisms that remain poorly understood. During systemic infection, Salmonella avoids NLRC4 inflammasome activation by down-regulating flagellin expression. Macrophages exhibit delayed NLRP3 inflammasome activation after Salmonella infection, suggesting that Salmonella may evade or prevent the rapid activation of the NLRP3 inflammasome. We therefore screened a Salmonella Typhimurium transposon library to identify bacterial factors that limit NLRP3 inflammasome activation. Surprisingly, absence of the Salmonella TCA enzyme aconitase induced rapid NLRP3 inflammasome activation. This inflammasome activation correlated with elevated levels of bacterial citrate, and required mitochondrial reactive oxygen species and bacterial citrate synthase. Importantly, Salmonella lacking aconitase displayed NLRP3- and caspase-1/11-dependent attenuation of virulence, and induced elevated serum IL-18 in wild-type mice. Together, our data link Salmonella genes controlling oxidative metabolism to inflammasome activation and suggest that NLRP3 inflammasome evasion promotes systemic Salmonella virulence.

Indexed as

Aconitate HydrataseAnimalsApoptosis Regulatory ProteinsBacterial Secretion SystemsCalcium-Binding ProteinsCarrier ProteinsCitrate (si)-SynthaseCitric Acid CycleGenes, BacterialImmune EvasionImmunityInflammasomesIsocitrate DehydrogenaseMiceMice, Inbred C57BLMitochondriaAconitate HydrataseApoptosis Regulatory ProteinsBacterial Secretion SystemsCalcium-Binding ProteinsCarrier ProteinsCitrate (si)-SynthaseInflammasomesIpaf protein, mouseIsocitrate DehydrogenaseNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseReactive Oxygen Species

Identifiers

PMID24638169
PMCPMC3978275
OpenAlexW2130743280

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.