Evidence map›Paper›PMID 27538572›Full record

ArticleJournal of leukocyte biology2016

A Pseudomonas aeruginosa hepta-acylated lipid A variant associated with cystic fibrosis selectively activates human neutrophils.

Shuvasree SenGupta, Lauren E Hittle, Robert K Ernst, Silvia M Uriarte, Thomas C Mitchell

Abstract readComparative Study
In one paragraph

Article in Journal of leukocyte biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

25 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Review
  3. Engineering low-endotoxin lipid A in a double auxotrophFrontiers in cellular and infection microbiology · 2026
    Article
  4. A critical role forProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. American journal of respiratory cell and molecular biology · 2024
    Article
  6. The multifaceted role of c-di-AMP signaling in the regulation ofFrontiers in cellular and infection microbiology · 2024
    Article
  7. Unravelling the mechanisms causing murepavadin resistance inFrontiers in cellular and infection microbiology · 2024
    Article
  8. Article
  9. Article
  10. Role of Host and Bacterial Lipids inFrontiers in immunology · 2022
    Review
  11. RecombinantInfection and immunity · 2021
    Article
  12. Lipopolysaccharide from biofilm-formingJournal of medical microbiology · 2021
    Article
  13. International journal of molecular sciences · 2021
    Review
  14. Article
  15. Human Neutrophil Granule Exocytosis in Response toPathogens (Basel, Switzerland) · 2020
    Article
  16. Whole Transcriptome Analysis Reveals ThatFrontiers in immunology · 2020
    Article
  17. The Role ofPathogens (Basel, Switzerland) · 2019
    Review
  18. Article
  19. Article
  20. Pseudomonas aeruginosa biofilm is a potent inducer of phagocyte hyperinflammation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019
    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

5 authors at 2 institutions in 1 country.

Shuvasree SenGuptaDepartment of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, USA.
Lauren E HittleDepartment of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, Maryland, USA.
Robert K ErnstDepartment of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, Maryland, USA rkernst@umaryland.edu.
Silvia M UriarteDepartment of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, USA; silvia.uriarte@louisville.edu.
Thomas C MitchellDepartment of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, USA; tom.mitchell@louisville.edu.
University of Louisville · USUniversity of Maryland, Baltimore · US

Funding

Granule exocytosis and neutrophil activationR00HL087924 · NHLBI · UNIVERSITY OF LOUISVILLE · PI URIARTE, SILVIA M · 2011 to 2013
$721k
Granule exocytosis and neutrophil activationK99HL087924 · NHLBI · UNIVERSITY OF LOUISVILLE · PI URIARTE, SILVIA M · 2009 to 2010
$258k
NHLBI NIH HHS K99 HL087924NHLBI NIH HHS R00 HL087924
6 · The paper itself

Abstract

Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) lung disease causes airway neutrophilia and hyperinflammation without effective bacterial clearance. We evaluated the immunostimulatory activities of lipid A, the membrane anchor of LPS, isolated from mutants of PA that synthesize structural variants, present in the airways of patients with CF, to determine if they correlate with disease severity and progression. In a subset of patients with a severe late stage of CF disease, a unique hepta-acylated lipid A, hepta-1855, is synthesized. In primary human cell cultures, we found that hepta-1855 functioned as a potent TLR4 agonist by priming neutrophil respiratory burst and stimulating strong IL-8 from monocytes and neutrophils. hepta-1855 also had a potent survival effect on neutrophils. However, it was less efficient in stimulating neutrophil granule exocytosis and also less potent in triggering proinflammatory TNF-α response from monocytes. In PA isolates that do not synthesize hepta-1855, a distinct CF-specific adaptation favors synthesis of a penta-1447 and hexa-1685 LPS mixture. We found that penta-1447 lacked immunostimulatory activity but interfered with inflammatory IL-8 synthesis in response to hexa-1685. Together, these observations suggest a potential contribution of hepta-1855 to maintenance of the inflammatory burden in late-stage CF by recruiting neutrophils via IL-8 and promoting their survival, an effect presumably amplified by the absence of penta-1447. Moreover, the relative inefficiency of hepta-1855 in triggering neutrophil degranulation may partly explain the persistence of PA in CF disease, despite extensive airway neutrophilia.

Indexed as

AcylationCells, CulturedChronic DiseaseCystic FibrosisDisease ProgressionExocytosisHEK293 CellsHumansLipid ALipopolysaccharidesNeutrophil ActivationOpportunistic InfectionsPneumonia, BacterialPseudomonas aeruginosaPseudomonas InfectionsRespiratory Bursthepta-1855hexa-1685Lipid Alipopolysaccharide, E coli O55-B5Lipopolysaccharidespenta-1447TLR4 protein, humanToll-Like Receptor 4chronic infectionimmunoevasioninflammationTLR4

Identifiers

PMID27538572
PMCPMC6608067
OpenAlexW2511131758

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.