Evidence map›Paper›PMID 14523045›Full record

ArticleThe Journal of clinical investigation2003

Identification of App1 as a regulator of phagocytosis and virulence of Cryptococcus neoformans.

Chiara Luberto, Beatriz Martinez-Mariño, Daniel Taraskiewicz, Benjamin Bolaños, Pasquale Chitano, Dena L Toffaletti, Gary M Cox, John R Perfect, Yusuf A Hannun, Edward Balish and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 4% 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

90 citing papers in PubMed, 1 synthesis or guideline pooled it, 150 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Antifungal Innate Immunity.Advances in experimental medicine and biology · 2025
    Review
  5. Review
  6. Review
  7. Inbred Mouse Models inJournal of fungi (Basel, Switzerland) · 2024
    Review
  8. Review
  9. Review
  10. Importance of Clinical Isolates inJournal of fungi (Basel, Switzerland) · 2023
    Review
  11. Review
  12. Sterylglucosides in Fungi.Journal of fungi (Basel, Switzerland) · 2022
    Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Macrophage Mediated Immunomodulation DuringFrontiers in cellular and infection microbiology · 2022
    Review
  18. Article
  19. Review
  20. Review

30 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

11 authors at 3 institutions in 3 countries.

Chiara LubertoDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA.
Beatriz Martinez-Mariño
Daniel Taraskiewicz
Benjamin Bolaños
Pasquale Chitano
Dena L Toffaletti
Gary M Cox
John R Perfect
Yusuf A Hannun
Edward Balish
Maurizio Del Poeta
Medical University of South Carolina · USDuke Medical Center · USUniversity of Puerto Rico, Medical Sciences Campus · PR

Funding

THE ROLE OF LACTOSYLCERAMIDE IN RENAL AGING AND DISEASEP20RR017677 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MAO, CUNGUI · 2002 to 2011
$23.4M
ROLE AND REGULATION OF PROTEIN KINASE C ISOENZYMESR01HL043707 · NHLBI · STATE UNIVERSITY NEW YORK STONY BROOK · PI HANNUN, YUSUF AWNI · 1990 to 2013
$4.6M
SIGNAL TRANSDUCTION PATHWAYS REGULATING VIRULENCEP01AI044975 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 1999 to 2003
$3.4M
GENTIC &MOLECULAR BIOLOGY OF VIRULENCE IN C. NEOFORMANSR01AI028388 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 1991 to 2004
$1.9M
Genetic molecular biology of virulence in C. neoformansR56AI028388 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 2006 to 2006
$389k
NCRR NIH HHS P20 RR017677NCRR NIH HHS RR17677-01NHLBI NIH HHS HL43707NHLBI NIH HHS R01 HL043707NIAID NIH HHS AI28388NIAID NIH HHS AI44975NIAID NIH HHS R01 AI028388NIAID NIH HHS R56 AI028388
6 · The paper itself

Abstract

Cryptococcus neoformans is a fungal pathogen that, after inhalation, can disseminate to the brain. Host alveolar macrophages (AMs) represent the first defense against the fungus. Once phagocytosed by AMs, fungal cells are killed by a concerted mechanism, involving the host-cellular response. If the cellular response is impaired, phagocytosis of the fungus may be detrimental for the host, since C. neoformans can grow within macrophages. Here, we identified a novel cryptococcal gene encoding antiphagocytic protein 1 (App1). App1 is a cryptococcal cytoplasmic protein that is secreted extracellularly and found in the serum of infected patients. App1 does not affect melanin production, capsule formation, or growth of C. neoformans. Treatment with recombinant App1 inhibited phagocytosis of fungal cells through a complement-mediated mechanism, and Deltaapp1 mutant is readily phagocytosed by AMs. Interestingly, the Deltaapp1 mutant strain showed a decreased virulence in mice deficient for complement C5 (A/Jcr), but it was hypervirulent in mice deficient for T and NK cells (Tgepsilon26). This study identifies App1 as a novel regulator of virulence for C. neoformans, and it highlights that internalization of fungal cells by AMs increases the dissemination of C. neoformans when the host cellular response is impaired.

Indexed as

PhagocytosisAnimalsBrainCryptococcosisCryptococcus neoformansFungal ProteinsKiller Cells, NaturalLungMacrophages, AlveolarMaleMiceT-LymphocytesVirulenceFungal Proteins

Identifiers

PMID14523045
PMCPMC198528
OpenAlexW2105045932

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.