Evidence map›Paper›PMID 22706306›Full record

ArticleThe Journal of clinical investigation2012

Fungal antioxidant pathways promote survival against neutrophils during infection.

Sixto M Leal, Chairut Vareechon, Susan Cowden, Brian A Cobb, Jean-Paul Latgé, Michelle Momany, Eric Pearlman

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

95 citing papers in PubMed, 145 citations in OpenAlex.

  1. Article
  2. Current issues in molecular biology · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Virulence ofbioRxiv : the preprint server for biology · 2025
    Article
  7. Article
  8. Review
  9. Resynthesis of Damaged Fe-S Cluster Proteins ProtectsJournal of fungi (Basel, Switzerland) · 2024
    Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Immunity to pathogenic fungi in the eye.Seminars in immunology · 2023
    Review

35 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

7 authors at 3 institutions in 2 countries.

Sixto M LealDepartment of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
Chairut Vareechon
Susan Cowden
Brian A Cobb
Jean-Paul Latgé
Michelle Momany
Eric Pearlman
Case Western Reserve University · USUniversity of Georgia · USInstitut Pasteur · FR

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
TISSUE CULTURE AND HYBRIDOMA MODULEP30EY011373 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Irina A Pikuleva · 1997 to 2026
$17.7M
Pathogenesis of Fungal KeratitisR01EY018612 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI PEARLMAN, ERIC · 2008 to 2022
$6.9M
Temporal and spatial profiling of gene expression during polar growth of AspergilR21AI074846 · NIAID · UNIVERSITY OF GEORGIA · PI MOMANY, MICHELLE · 2008 to 2009
$323k
The Pathogenesis of Aspergillus KeratitisF31EY019841 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI LEAL, SIXTO MANUEL · 2009 to 2012
$154k
NEI NIH HHS F31 EY019841NEI NIH HHS P30 EY011373NEI NIH HHS R01 EY018612NIAID NIH HHS R21 AI074846NIAID NIH HHS R21 AI074846-02NIGMS NIH HHS T32 GM007250
6 · The paper itself

Abstract

Filamentous fungi are a common cause of blindness and visual impairment worldwide. Using both murine model systems and in vitro human neutrophils, we found that NADPH oxidase produced by neutrophils was essential to control the growth of Aspergillus and Fusarium fungi in the cornea. We demonstrated that neutrophil oxidant production and antifungal activity are dependent on CD18, but not on the β-glucan receptor dectin-1. We used mutant A. fumigatus strains to show that the reactive oxygen species-sensing transcription factor Yap1, superoxide dismutases, and the Yap1-regulated thioredoxin antioxidant pathway are each required for protection against neutrophil-mediated oxidation of hyphae as well as optimal survival of fungal hyphae in vivo. We also demonstrated that thioredoxin inhibition using the anticancer drug PX-12 increased the sensitivity of fungal hyphae to both H2O2- and neutrophil-mediated killing in vitro. Additionally, topical application of PX-12 significantly enhanced neutrophil-mediated fungal killing in infected mouse corneas. Cumulatively, our data reveal critical host oxidative and fungal anti-oxidative mediators that regulate hyphal survival during infection. Further, these findings also indicate that targeting fungal anti-oxidative defenses via PX-12 may represent an efficacious strategy for treating fungal infections.

Indexed as

Microbial ViabilityAnimalsAntioxidantsAspergillosisAspergillus flavusAspergillus fumigatusCD18 AntigensCells, CulturedCorneaEnzyme ActivationFungal ProteinsFusariosisFusariumHost-Pathogen InteractionsHumansKeratitisAntioxidantsCD18 AntigensFungal ProteinsNADPH OxidasesNitric OxideNitric Oxide Synthase Type IINos2 protein, mousePeroxidaseReactive Oxygen SpeciesSuperoxide DismutaseThioredoxinsTranscription Factors

Identifiers

PMID22706306
PMCPMC3534057
OpenAlexW2095648038

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.