Evidence map›Paper›PMID 25815810›Full record

ArticlePLoS genetics2015

Systems biology of tissue-specific response to Anaplasma phagocytophilum reveals differentiated apoptosis in the tick vector Ixodes scapularis.

Nieves Ayllón, Margarita Villar, Ruth C Galindo, Katherine M Kocan, Radek Šíma, Juan A López, Jesús Vázquez, Pilar Alberdi, Alejandro Cabezas-Cruz, Petr Kopáček and 1 more

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 2 pooled it
13.3field-weighted citation impact, top 1% 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, 2 syntheses or guidelines pooled it, 129 citations in OpenAlex.

  1. Guideline
  2. Guideline
  3. Article
  4. Article
  5. Mitochondrial Dysfunction inTransboundary and emerging diseases · 2026
    Review
  6. ATF6 enables pathogen infection in ticks by inducingProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Review
  8. Apoptosis and autophagy promoteFrontiers in microbiology · 2025
    Article
  9. Article
  10. Perilipin1 inhibitsMicrobiology spectrum · 2024
    Article
  11. Article
  12. Article
  13. Frontiers in microbiology · 2024
    Article
  14. Functional characterization ofFrontiers in cellular and infection microbiology · 2024
    Article
  15. Towards modelling tick-virus interactions using the weakly pathogenicFrontiers in cellular and infection microbiology · 2024
    Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

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 5 institutions in 5 countries.

Nieves AyllónSaBio. Instituto de Investigación en Recursos Cinegéticos IREC, CSIC-UCLM-JCCM, Ciudad Real, Spain.
Margarita VillarSaBio. Instituto de Investigación en Recursos Cinegéticos IREC, CSIC-UCLM-JCCM, Ciudad Real, Spain.
Ruth C GalindoSaBio. Instituto de Investigación en Recursos Cinegéticos IREC, CSIC-UCLM-JCCM, Ciudad Real, Spain; Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma, United States of America.
Katherine M KocanDepartment of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma, United States of America.
Radek ŠímaInstitute of Parasitology, Biology Centre, Academy of Sciences of the Czech Republic, České Budějovice, The Czech Republic.
Juan A LópezCentro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Jesús VázquezCentro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Pilar AlberdiSaBio. Instituto de Investigación en Recursos Cinegéticos IREC, CSIC-UCLM-JCCM, Ciudad Real, Spain.
Alejandro Cabezas-CruzSaBio. Instituto de Investigación en Recursos Cinegéticos IREC, CSIC-UCLM-JCCM, Ciudad Real, Spain; Center for Infection and Immunity of Lille (CIIL), Université Lille Nord de France, Institut Pasteur de Lille, Lille, France.
Petr KopáčekInstitute of Parasitology, Biology Centre, Academy of Sciences of the Czech Republic, České Budějovice, The Czech Republic.
José de la FuenteSaBio. Instituto de Investigación en Recursos Cinegéticos IREC, CSIC-UCLM-JCCM, Ciudad Real, Spain; Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma, United States of America.
Instituto de Investigación en Recursos Cinegéticos · ESInstitute of Parasitology of the Slovak Academy of Sciences · SKOklahoma State University · USSpanish National Centre for Cardiovascular Research · ESInserm · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Anaplasma phagocytophilum is an emerging pathogen that causes human granulocytic anaplasmosis. Infection with this zoonotic pathogen affects cell function in both vertebrate host and the tick vector, Ixodes scapularis. Global tissue-specific response and apoptosis signaling pathways were characterized in I. scapularis nymphs and adult female midguts and salivary glands infected with A. phagocytophilum using a systems biology approach combining transcriptomics and proteomics. Apoptosis was selected for pathway-focused analysis due to its role in bacterial infection of tick cells. The results showed tissue-specific differences in tick response to infection and revealed differentiated regulation of apoptosis pathways. The impact of bacterial infection was more pronounced in tick nymphs and midguts than in salivary glands, probably reflecting bacterial developmental cycle. All apoptosis pathways described in other organisms were identified in I. scapularis, except for the absence of the Perforin ortholog. Functional characterization using RNA interference showed that Porin knockdown significantly increases tick colonization by A. phagocytophilum. Infection with A. phagocytophilum produced complex tissue-specific alterations in transcript and protein levels. In tick nymphs, the results suggested a possible effect of bacterial infection on the inhibition of tick immune response. In tick midguts, the results suggested that A. phagocytophilum infection inhibited cell apoptosis to facilitate and establish infection through up-regulation of the JAK/STAT pathway. Bacterial infection inhibited the intrinsic apoptosis pathway in tick salivary glands by down-regulating Porin expression that resulted in the inhibition of Cytochrome c release as the anti-apoptotic mechanism to facilitate bacterial infection. However, tick salivary glands may promote apoptosis to limit bacterial infection through induction of the extrinsic apoptosis pathway. These dynamic changes in response to A. phagocytophilum in I. scapularis tissue-specific transcriptome and proteome demonstrated the complexity of the tick response to infection and will contribute to characterize gene regulation in ticks.

Indexed as

Systems BiologyAnaplasma phagocytophilumAnaplasmosisAnimalsApoptosisCell DifferentiationFemaleGene Expression RegulationHumansInsect VectorsIxodesOrgan SpecificityRNA InterferenceSalivary GlandsSignal TransductionTranscriptome

Identifiers

PMID25815810
PMCPMC4376793
OpenAlexW1971058819

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.