Evidence map›Paper›PMID 30248149›Full record

ArticlePLoS pathogens2018

NLRP6 negatively regulates pulmonary host defense in Gram-positive bacterial infection through modulating neutrophil recruitment and function.

Laxman Ghimire, Sagar Paudel, Liliang Jin, Pankaj Baral, Shanshan Cai, Samithamby Jeyaseelan

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

65 citing papers in PubMed, 100 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Supramolecular Assemblies Drive Activation of Inflammasomes.Advances in experimental medicine and biology · 2026
    Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. NLRP inflammasomes in health and disease.Molecular biomedicine · 2024
    Review
  18. Article
  19. A mouse model to distinguish NLRP6-mediated inflammasome-dependent and -independent functions.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  20. Review

5 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

6 authors at 1 institution in 1 country.

Laxman GhimireLung Biology Laboratory, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University (LSU), Baton Rouge, LA, United States of America.
Sagar PaudelLung Biology Laboratory, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University (LSU), Baton Rouge, LA, United States of America.
Liliang JinLung Biology Laboratory, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University (LSU), Baton Rouge, LA, United States of America.
Pankaj BaralLung Biology Laboratory, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University (LSU), Baton Rouge, LA, United States of America.
Shanshan CaiLung Biology Laboratory, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University (LSU), Baton Rouge, LA, United States of America.
Samithamby JeyaseelanLung Biology Laboratory, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University (LSU), Baton Rouge, LA, United States of America.ORCID 0000-0002-1959-1328
Louisiana State University · US

Funding

Neutrophil Accumulation in Bacterial PneumoniaR01HL091958 · NHLBI · LOUISIANA STATE UNIV A&M COL BATON ROUGE · PI JEYASEELAN, SAMITHAMBY · 2008 to 2017
$3.8M
Neutrophil Function in Bacterial PneumoniaR01AI113720 · NIAID · LOUISIANA STATE UNIV A&M COL BATON ROUGE · PI JEYASEELAN, SAMITHAMBY · 2015 to 2019
$1.9M
Innate Immunity in Pneumonic SepsisR01HL133336 · NHLBI · UNIVERSITY OF WASHINGTON · PI CAI, SHANSHAN · 2017 to 2020
$1.6M
Role of Lung Mesenchymal Stem Cells in Pneumonia-induced SepsisR21AI133681 · NIAID · LOUISIANA STATE UNIV A&M COL BATON ROUGE · PI JEYASEELAN, SAMITHAMBY · 2018 to 2019
$407k
Role of Innate Immunity in Pneumonic SepsisF31HL137287 · NHLBI · LOUISIANA STATE UNIV A&M COL BATON ROUGE · PI PAUDEL, SAGAR · 2017 to 2019
$105k
NHLBI NIH HHS F31 HL137287NHLBI NIH HHS R01 HL091958NHLBI NIH HHS R01 HL133336NIAID NIH HHS R01 AI113720NIAID NIH HHS R21 AI133681
6 · The paper itself

Abstract

Gram-positive bacteria, including Staphylococcus aureus are endemic in the U.S., which cause life-threatening necrotizing pneumonia. Neutrophils are known to be critical for clearance of S. aureus infection from the lungs and extrapulmonary organs. Therefore, we investigated whether the NLRP6 inflammasome regulates neutrophil-dependent host immunity during pulmonary S. aureus infection. Unlike their wild-type (WT) counterparts, NLRP6 knockout (KO) mice were protected against pulmonary S. aureus infection as evidenced by their higher survival rate and lower bacterial burden in the lungs and extrapulmonary organs. In addition, NLRP6 KO mice displayed increased neutrophil recruitment following infection, and when neutrophils were depleted the protective effect was lost. Furthermore, neutrophils from the KO mice demonstrated enhanced intracellular bacterial killing and increased NADPH oxidase-dependent ROS production. Intriguingly, we found higher NK cell-mediated IFN-γ production in KO mouse lungs, and treatment with IFN-γ was found to enhance the bactericidal ability of WT and KO neutrophils. The NLRP6 KO mice also displayed decreased pyroptosis and necroptosis in the lungs following infection. Blocking of pyroptosis and necroptosis in WT mice resulted in increased survival, reduced bacterial burden in the lungs, and attenuated cytokine production. Taken together, these novel findings show that NLRP6 serves as a negative regulator of neutrophil-mediated host defense during Gram-positive bacterial infection in the lungs through regulating both neutrophil influx and function. These results also suggest that blocking NLRP6 to augment neutrophil-associated bacterial clearance should be considered as a potential therapeutic intervention strategy for treatment of S. aureus pneumonia.

Indexed as

AnimalsCD4-Positive T-LymphocytesFemaleHost-Pathogen InteractionsHumansInflammasomesInterferon-gammaKiller Cells, NaturalLungMaleMiceMice, Inbred C57BLMice, KnockoutNeutrophil InfiltrationPneumonia, NecrotizingPneumonia, StaphylococcalInflammasomesInterferon-gammaNod-like receptor pyrin domain-containing protein 6, mouseReactive Oxygen SpeciesReceptors, Cell Surface

Identifiers

PMID30248149
PMCPMC6171945
OpenAlexW2892982134

What OpenQuestion holds

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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.