CoChat
Sign Up
Cited by 370Neutrophil, Myeloperoxidase and Oxidative MechanismsImmunodeficiency and Autoimmune DisordersAntifungal resistance and susceptibility

Absence of Respiratory Burst in X-linked Chronic Granulomatous Disease Mice Leads to Abnormalities in Both Host Defense and Inflammatory Response to Aspergillus fumigatus

Open access
Morgenstern, David E., Gifford, Mary A.C., Li, Ling Lin, Doerschuk, Claire M., Dinauer, Mary C.·1997·The Journal of Experimental Medicine
DOI 10.1084/jem.185.2.207PMC PMC2196125
Open this paper in CoChat — free accountOpen PDF

Abstract

Mice with X-linked chronic granulomatous disease (CGD) generated by targeted disruption of the gp91phox subunit of the NADPH-oxidase complex (X-CGD mice) were examined for their response to respiratory challenge with Aspergillus fumigatus. This opportunistic fungal pathogen causes infection in CGD patients due to the deficient generation of neutrophil respiratory burst oxidants important for damaging A. fumigatus hyphae. Alveolar macrophages from X-CGD mice were found to kill A. fumigatus conidia in vitro as effectively as alveolar macrophages from wild-type mice. Pulmonary disease in X-CGD mice was observed after administration of doses ranging from 10(5) to 48 spores, none of which produced disease in wild-type mice. Higher doses produced a rapidly fatal bronchopneumonia in X-CGD mice, whereas progression of disease was slower at lower doses, with development of chronic inflammatory lesions. Marked differences were also observed in the response of X-CGD mice to the administration of sterilized Aspergillus hyphae into the lung. Within 24 hours of administration, X-CGD mice had significantly higher numbers of alveolar neutrophils and increased expression of the proinflammatory cytokines IL-1 beta and TNF-alpha relative to the responses seen in wild-type mice. By one week after administration, pulmonary inflammation was resolving in wild-type mice, whereas X-CGD mice developed chronic granulomatous lesions that persisted for at least six weeks. This is the first experimental evidence that chronic inflammation in CGD does not always result from persistent infection, and suggests that the clinical manifestations of this disorder reflect both impaired microbial killing as well as other abnormalities in the inflammatory response in the absence of a respiratory burst.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1084/jem.185.2.207

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Killing of Aspergillus conidia by AMs is dependent on both oxidative and nonoxidative mechanisms.

    “Although killing of Aspergillus conidia by AMs is undoubtedly dependent on both oxidative and nonoxidative mechanisms (240, 241)”

    From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [240]

  • Much of the discrepancy in the literature on killing of Aspergillus conidia by AMs is related to differences in study endpoints, methodology of killing assessment, moiety of infection, infection time points, NADPH oxidase knockout mouse strains, and method of immunosuppression.

    “much of the discrepancy in the literature is related to differences in study endpoints (e.g., inhibition of growth versus killing), methodology of killing assessment (e.g., CFU plating versus conidial germination), moiety of infection, infection time points, NADPH oxidase knockout mouse strains, and method of immunosuppression used (203, 240–245).”

    From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [240]

  • Unlike the neutropenic mouse model, extensive signs of chronic inflammation remained evident in the X-CGD mice post-day 14.

    “Unlike the neutropenic mouse model, extensive signs of chronic inflammation remained evident in the X-CGD mice post-day 14, consistent with previously reported results in these animals [45].”

    From A Sterol-Regulatory Element Binding Protein Is Required for Cell Polarity, Hypoxia Adaptation, Azole Drug Resistance, and Virulence in Aspergillus fumigatus (2008) · cites this paper as [45]

  • X-CGD gp91phox−/− mice exhibit a hyper-inflammatory response when exposed to A. fumigatus and other Aspergillus species.

    “These mice exhibit a hyper-inflammatory response when exposed to A. fumigatus and other Aspergillus species.”

    From A Sterol-Regulatory Element Binding Protein Is Required for Cell Polarity, Hypoxia Adaptation, Azole Drug Resistance, and Virulence in Aspergillus fumigatus (2008) · cites this paper as [45]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

2 of the 51 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. [8]Dixon DM Polack A Walsh TJ Fungus dosedependent primary pulmonary aspergillosis Infect Immun 1989 57 1452 1456 2651308 PMC313298
  2. [19]Pollock J Williams D Gifford M Li L Du X Fisherman J Orkin S Doerschuk C Dinauer M Mouse model of X-linked chronic granulomatous disease, an inherited defect in phagocytes superoxide production Nat Genet 1995 9 202 209 7719350
  3. [25]Curnutte, J. 1992. Disorders of granulocyte function and granulopoiesis. In Hematology of Infancy and Childhood, 4th ed. N. Oski, editor, W.B. Saunders Company, Philadelphia. 904–937.

Cited by

Sorted by citations

Related

Authors
Morgenstern, D. E., Gifford, M. A. C., Li, L. L., Doerschuk, C. M., & Dinauer, M. C.
Affiliations
Riley Hospital for Children (US)
ORCID
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
1997-01-20
Volume
185
Issue
2
Pages
207-218
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.185.2.207
PMC
PMC2196125
OpenAlex
W2138396364
Cited by
370
References
51
Citations by year
2026: 5 · 2025: 5 · 2024: 2 · 2023: 4 · 2022: 9 · 2021: 13 · 2020: 7 · 2019: 11 · 2018: 11 · 2017: 18 · 2016: 12 · 2015: 11 · 2014: 22 · 2013: 18 · 2012: 17
FWCI
5.40
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion, cc-by-nc-sa)
  • UNC Libraries
Funders
  • Arthritis Foundation
  • National Institutes of Health (5r01hl052565-05)
  • National Heart, Lung, and Blood Institute (R01 HL52565)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Keywords
X-linked chronic granulomatous disease, Aspergillus fumigatus, respiratory burst, NADPH oxidase, gp91phox, alveolar macrophages, neutrophils, lung inflammation, IL-1β, TNF-α, fungal infection, bronchopneumonia
MeSH terms
NADPH Oxidase 2, Animals, Aspergillus fumigatus, Granulomatous Disease, Chronic, Inflammation, Genetic Linkage, Lung Diseases, Membrane Glycoproteins, Phagocytosis, X Chromosome, Cytokines, Macrophages, Alveolar, Respiratory Burst, NADPH Oxidases, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review