Evidence map›Paper›PMID 22761577›Full record

ArticlePLoS pathogens2012

The rhoptry proteins ROP18 and ROP5 mediate Toxoplasma gondii evasion of the murine, but not the human, interferon-gamma response.

Wendy Niedelman, Daniel A Gold, Emily E Rosowski, Joris K Sprokholt, Daniel Lim, Ailan Farid Arenas, Mariane B Melo, Eric Spooner, Michael B Yaffe, Jeroen P J Saeij

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.

0numbers the graph read from it
0cells of the map it votes in
140citing papers in PubMed
–field-weighted citation impact, top 95% 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

140 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. A Live Attenuated AP2X-1-DeficientAnimals : an open access journal from MDPI · 2026
    Article
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  6. Article
  7. Cysteine-S-nitrosylation inhibits Rop5-mediated immune evasion inbioRxiv : the preprint server for biology · 2025
    Article
  8. Article
  9. mBio · 2025
    Article
  10. Article
  11. Vaccines · 2025
    Review
  12. Review
  13. Article
  14. Article
  15. Frontiers in immunology · 2025
    Article
  16. Article
  17. International journal of molecular sciences · 2024
    Article
  18. Article
  19. Article
  20. Article

80 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

10 authors at 3 institutions in 3 countries.

Wendy NiedelmanDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Daniel A Gold
Emily E Rosowski
Joris K Sprokholt
Daniel Lim
Ailan Farid Arenas
Mariane B Melo
Eric Spooner
Michael B Yaffe
Jeroen P J Saeij
Massachusetts Institute of Technology · USUniversity of Quindío · COWageningen University & Research · NL

Funding

PRE-DOCTORAL TRAINING IN THE BIOLOGICAL SCIENCEST32GM007287 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELL, STEPHEN P., KEATING, AMY E · 1985 to 2019
$40.8M
Systems Biology of Cell Decision ProcessesP50GM068762 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YAFFE, MICHAEL B · 2003 to 2012
$32.3M
NEUTROPHIL PRIMING IN TRAUMA AND SEPSISR01GM059281 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YAFFE, MICHAEL B · 1999 to 2011
$4.2M
Toxoplasma strain-specific modulation of mouse immune cellsR01AI080621 · NIAID · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SAEIJ, JEROEN · 2009 to 2018
$3.6M
CIHRNIAID NIH HHS R01 AI080621NIAID NIH HHS R01-AI080621NIGMS NIH HHS 5-T32-GM007287-33NIGMS NIH HHS P50 GM068762NIGMS NIH HHS P50-GM68762NIGMS NIH HHS R01 GM059281NIGMS NIH HHS R01-GM59281NIGMS NIH HHS T32 GM007287
6 · The paper itself

Abstract

The obligate intracellular parasite Toxoplasma gondii secretes effector proteins into the host cell that manipulate the immune response allowing it to establish a chronic infection. Crosses between the types I, II and III strains, which are prevalent in North America and Europe, have identified several secreted effectors that determine strain differences in mouse virulence. The polymorphic rhoptry protein kinase ROP18 was recently shown to determine the difference in virulence between type I and III strains by phosphorylating and inactivating the interferon-γ (IFNγ)-induced immunity-related GTPases (IRGs) that promote killing by disrupting the parasitophorous vacuole membrane (PVM) in murine cells. The polymorphic pseudokinase ROP5 determines strain differences in virulence through an unknown mechanism. Here we report that ROP18 can only inhibit accumulation of the IRGs on the PVM of strains that also express virulent ROP5 alleles. In contrast, specific ROP5 alleles can reduce IRG coating even in the absence of ROP18 expression and can directly interact with one or more IRGs. We further show that the allelic combination of ROP18 and ROP5 also determines IRG evasion and virulence of strains belonging to other lineages besides types I, II and III. However, neither ROP18 nor ROP5 markedly affect survival in IFNγ-activated human cells, which lack the multitude of IRGs present in murine cells. These findings suggest that ROP18 and ROP5 have specifically evolved to block the IRGs and are unlikely to have effects in species that do not have the IRG system, such as humans.

Indexed as

AnimalsBlotting, WesternChromatography, High Pressure LiquidFluorescent Antibody TechniqueGTP PhosphohydrolasesHigh-Throughput Screening AssaysHumansImmune EvasionImmunoprecipitationInterferon-gammaMass SpectrometryMiceProtein Serine-Threonine KinasesProtozoan ProteinsReverse Transcriptase Polymerase Chain ReactionSpecies SpecificityGTP PhosphohydrolasesInterferon-gammaProtein Serine-Threonine KinasesProtozoan ProteinsROP18 protein, Toxoplasma gondii

Identifiers

PMID22761577
PMCPMC3386190
OpenAlexW1567048727

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.