Evidence map›Paper›PMID 18927622›Full record

ArticlePLoS pathogens2008

Control of parasitophorous vacuole expansion by LYST/Beige restricts the intracellular growth of Leishmania amazonensis.

Jude Wilson, Chau Huynh, Kathleen A Kennedy, Diane M Ward, Jerry Kaplan, Alan Aderem, Norma W Andrews

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.2field-weighted citation impact, top 9% 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

34 citing papers in PubMed, 72 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Lysosomal trafficking regulator restricts intracellular growth ofFrontiers in cellular and infection microbiology · 2023
    Article
  5. iScience · 2022
    Article
  6. Article
  7. Article
  8. Revisiting the Mechanisms of Immune Evasion Employed by Human Parasites.Frontiers in cellular and infection microbiology · 2021
    Review
  9. Review
  10. Article
  11. Review
  12. International journal of microbiology · 2020
    Article
  13. TheThe Yale journal of biology and medicine · 2019
    Review
  14. Article
  15. CD4Frontiers in cellular and infection microbiology · 2019
    Article
  16. Autophagic Induction Greatly EnhancesFrontiers in microbiology · 2018
    Article
  17. Frontiers in microbiology · 2018
    Review
  18. Survival Mechanisms Used by SomeFrontiers in immunology · 2017
    Review
  19. Article
  20. 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

7 authors at 3 institutions in 1 country.

Jude WilsonSection of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Chau Huynh
Kathleen A Kennedy
Diane M Ward
Jerry Kaplan
Alan Aderem
Norma W Andrews
Yale University · USInstitute for Systems Biology · USUniversity of Utah · US

Funding

Regulated exocytosis of lysosomes and plasma membrane repairR01GM064625 · NIGMS · YALE UNIVERSITY · PI ANDREWS, NORMA WINDSOR, SONG, WENXIA · 2002 to 2020
$6.3M
Lyosome Mediated Cell Invasion by Trypanosoma CruziR37AI034867 · NIAID · YALE UNIVERSITY · PI ANDREWS, NORMA WINDSOR · 2003 to 2012
$4.5M
Recognition of Bacterial Flagellin by MacrophagesR01AI052286 · NIAID · SEATTLE BIOMEDICAL RESEARCH INSTITUTE · PI ADEREM, ALAN A · 2002 to 2011
$4.2M
Molecular Determinants of Intracellular Survival and Replication in LeishmaniaR01AI067979 · NIAID · YALE UNIVERSITY · PI ANDREWS, NORMA WINDSOR · 2007 to 2018
$3.8M
RECEPTOR MEDIATED ENDOCYTOSIS IN ALVEOLAR MACROPHAGESR37HL026922 · NHLBI · UNIVERSITY OF UTAH · PI KAPLAN, JERRY · 1997 to 2006
$2.5M
RECEPTOR MEDIATED ENDOCYTOSIS IN ALVEOLAR MACROPHAGESR01HL026922 · NHLBI · UNIVERSITY OF UTAH · PI WARD, DIANE MCVEY · 1985 to 2012
$1.9M
NHLBI NIH HHS R01 HL026922NHLBI NIH HHS R37 HL026922NHLBI NIH HHS R37HL26922NIAID NIH HHS 5R01AI05228NIAID NIH HHS R01 AI052286NIAID NIH HHS R01 AI067979NIAID NIH HHS R37 AI034867NIAID NIH HHS R37AI34867NIGMS NIH HHS R01 GM064625NIGMS NIH HHS R01GM64625
6 · The paper itself

Abstract

The intracellular protozoan Leishmania replicates in parasitophorous vacuoles (PV) that share many features with late endosomes/lysosomes. L. amazonensis PVs expand markedly during infections, but the impact of PV size on parasite intracellular survival is still unknown. Here we show that host cells infected with L. amazonensis upregulate transcription of LYST/Beige, which was previously shown to regulate lysosome size. Mutations in LYST/Beige caused further PV expansion and enhanced L. amazonensis replication. In contrast, LYST/Beige overexpression led to small PVs that did not sustain parasite growth. Treatment of LYST/Beige over-expressing cells with vacuolin-1 reversed this phenotype, expanding PVs and promoting parasite growth. The opposite was seen with E-64d, which reduced PV size in LYST-Beige mutant cells and inhibited L. amazonensis replication. Enlarged PVs appear to protect parasites from oxidative damage, since inhibition of nitric oxide synthase had no effect on L. amazonensis viability within large PVs, but enhanced their growth within LYST/Beige-induced small PVs. Thus, the upregulation of LYST/Beige in infected cells functions as a host innate response to limit parasite growth, by reducing PV volume and inhibiting intracellular survival.

Indexed as

AnimalsApoptosisCells, CulturedCell SurvivalHost-Parasite InteractionsImmunity, InnateIntracellular Signaling Peptides and ProteinsLeishmaniaLeishmaniasisMacrophagesMiceMice, Inbred C57BLNitric OxideOrganelle SizeProteinsRNA, MessengerIntracellular Signaling Peptides and ProteinsLyst protein, mouseNitric OxideProteinsRNA, MessengerVesicular Transport Proteins

Identifiers

PMID18927622
PMCPMC2562527
OpenAlexW2083723305

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.