Evidence map›Paper›PMID 24549323›Full record

ArticleInfection and immunity2014

NADPH oxidase promotes neutrophil extracellular trap formation in pulmonary aspergillosis.

Marc Röhm, Melissa J Grimm, Anthony C D'Auria, Nikolaos G Almyroudis, Brahm H Segal, Constantin F Urban

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 2 pooled it
5.9field-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

98 citing papers in PubMed, 2 syntheses or guidelines pooled it, 161 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Fungal Infections in Disorders of Inborn Errors of Immunity.Clinical reviews in allergy & immunology · 2026
    Review
  4. Current issues in molecular biology · 2026
    Article
  5. A pathology-to-single-cell framework links SPP1Journal of translational medicine · 2026
    Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Interplay of Cytokines and Chemokines in Aspergillosis.Journal of fungi (Basel, Switzerland) · 2024
    Review
  14. Dying to Defend: Neutrophil Death Pathways and their Implications in Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
  15. Aspergillus and the Lung.Seminars in respiratory and critical care medicine · 2024
    Review
  16. International journal of molecular sciences · 2023
    Article
  17. Review
  18. Article
  19. Article
  20. Review

38 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 2 institutions in 2 countries.

Marc RöhmDepartment of Clinical Microbiology, Umeå University, Umeå, Sweden.
Melissa J Grimm
Anthony C D'Auria
Nikolaos G Almyroudis
Brahm H Segal
Constantin F Urban
Roswell Park Comprehensive Cancer Center · USUmeå University · SE

Funding

Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MARK G FRATTINI · 1985 to 2026
$116.6M
Role of NADPH Oxidase in Regulating InflammationR01AI079253 · NIAID · ROSWELL PARK CANCER INSTITUTE CORP · PI SEGAL, BRAHM H. · 2009 to 2013
$2.1M
NCI NIH HHS CA016056NCI NIH HHS P30 CA016056NIAID NIH HHS R01 AI079253
6 · The paper itself

Abstract

NADPH oxidase is a crucial enzyme in antimicrobial host defense and in regulating inflammation. Chronic granulomatous disease (CGD) is an inherited disorder of NADPH oxidase in which phagocytes are defective in generation of reactive oxidant intermediates. Aspergillus species are ubiquitous, filamentous fungi, which can cause invasive aspergillosis, a major cause of morbidity and mortality in CGD, reflecting the critical role for NADPH oxidase in antifungal host defense. Activation of NADPH oxidase in neutrophils can be coupled to the release of proteins and chromatin that comingle in neutrophil extracellular traps (NETs), which can augment extracellular antimicrobial host defense. NETosis can be driven by NADPH oxidase-dependent and -independent pathways. We therefore undertook an analysis of whether NADPH oxidase was required for NETosis in Aspergillus fumigatus pneumonia. Oropharyngeal instillation of live Aspergillus hyphae induced neutrophilic pneumonitis in both wild-type and NADPH oxidase-deficient (p47(phox-/-)) mice which had resolved in wild-type mice by day 5 but progressed in p47(phox-/-) mice. NETs, identified by immunostaining, were observed in lungs of wild-type mice but were absent in p47(phox-/-) mice. Using bona fide NETs and nuclear chromatin decondensation as an early NETosis marker, we found that NETosis required a functional NADPH oxidase in vivo and ex vivo. In addition, NADPH oxidase increased the proportion of apoptotic neutrophils. Together, our results show that NADPH oxidase is required for pulmonary clearance of Aspergillus hyphae and generation of NETs in vivo. We speculate that dual modulation of NETosis and apoptosis by NADPH oxidase enhances antifungal host defense and promotes resolution of inflammation upon infection clearance.

Indexed as

AnimalsAspergillus fumigatusGene Expression Regulation, EnzymologicHyphaeInflammationMiceMice, KnockoutNADPH OxidasesNeutrophilsPulmonary AlveoliPulmonary AspergillosisNADPH Oxidases

Identifiers

PMID24549323
PMCPMC3993456
OpenAlexW2137625680

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.