Evidence map›Paper›PMID 25375322›Full record

ArticlePLoS neglected tropical diseases2014

Engineering attenuated virulence of a Theileria annulata-infected macrophage.

Nadia Echebli, Moez Mhadhbi, Marie Chaussepied, Catherine Vayssettes, James P Di Santo, Mohamed Aziz Darghouth, Gordon Langsley

Open access · goldAbstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.9field-weighted citation impact, top 31% 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

9 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. A Culture-Adapted Strain ofFrontiers in cellular and infection microbiology · 2022
    Article
  3. Frontiers in cell and developmental biology · 2021
    Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. 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 6 institutions in 2 countries.

Nadia EchebliLaboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médicine, Université Paris Descartes - Sorbonne Paris Cité, Paris, France; Inserm U1016, Cnrs UMR8104, Cochin Institute, Paris, France.
Moez MhadhbiLaboratoire de Parasitologie, Ecole Nationale de Médecine Vétérinaire, Sidi Thabet, Tunisia.
Marie ChaussepiedLaboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médicine, Université Paris Descartes - Sorbonne Paris Cité, Paris, France; Inserm U1016, Cnrs UMR8104, Cochin Institute, Paris, France.
Catherine VayssettesLaboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médicine, Université Paris Descartes - Sorbonne Paris Cité, Paris, France; Inserm U1016, Cnrs UMR8104, Cochin Institute, Paris, France.
James P Di SantoInnate Immunity Unit, Department of Immunology, Pasteur Institute, Paris, France; Inserm U688, Pasteur Institute, Paris, France.
Mohamed Aziz DarghouthLaboratoire de Parasitologie, Ecole Nationale de Médecine Vétérinaire, Sidi Thabet, Tunisia; Institution de la Recherche et de l'Enseignement Supérieur Agricoles, Tunis, Tunisia.
Gordon LangsleyLaboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médicine, Université Paris Descartes - Sorbonne Paris Cité, Paris, France; Inserm U1016, Cnrs UMR8104, Cochin Institute, Paris, France.
Inserm · FRInstitut Cochin · FRInstitution de la Recherche et de l’Enseignement Supérieur Agricoles · TNInstitut Pasteur · FRSorbonne Paris Cité · FRUniversité Paris Cité · FR

Funding

Wellcome TrustWellcome Trust 075820/A/04/Z
6 · The paper itself

Abstract

Live attenuated vaccines are used to combat tropical theileriosis in North Africa, the Middle East, India, and China. The attenuation process is empirical and occurs only after many months, sometimes years, of in vitro culture of virulent clinical isolates. During this extensive culturing, attenuated lines lose their vaccine potential. To circumvent this we engineered the rapid ablation of the host cell transcription factor c-Jun, and within only 3 weeks the line engineered for loss of c-Jun activation displayed in vitro correlates of attenuation such as loss of adhesion, reduced MMP9 gelatinase activity, and diminished capacity to traverse Matrigel. Specific ablation of a single infected host cell virulence trait (c-Jun) induced a complete failure of Theileria annulata-transformed macrophages to disseminate, whereas virulent macrophages disseminated to the kidneys, spleen, and lungs of Rag2/γC mice. Thus, in this heterologous mouse model loss of c-Jun expression led to ablation of dissemination of T. annulata-infected and transformed macrophages. The generation of Theileria-infected macrophages genetically engineered for ablation of a specific host cell virulence trait now makes possible experimental vaccination of calves to address how loss of macrophage dissemination impacts the disease pathology of tropical theileriosis.

Indexed as

VaccinationAnimalsCell AdhesionCell LineFemaleFibronectinsGenetic EngineeringKidneyLungMacrophagesMaleMiceMutationProto-Oncogene Proteins c-junProtozoan VaccinesSpleenFibronectinsProto-Oncogene Proteins c-junProtozoan VaccinesVaccines, Attenuated

Identifiers

PMID25375322
PMCPMC4222746
OpenAlexW1995567981

What Socratic 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 Socratic graph.