Evidence map›Paper›PMID 25070851›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2014

The DNA sensor, cyclic GMP-AMP synthase, is essential for induction of IFN-β during Chlamydia trachomatis infection.

Yugen Zhang, Laxmi Yeruva, Anthony Marinov, Daniel Prantner, Priscilla B Wyrick, Vladimir Lupashin, Uma M Nagarajan

Open access · greenAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed, 1 pooled it
6.1field-weighted citation impact, top 3% 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

110 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Article
  6. Article
  7. Journal of inflammation research · 2026
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Recognition ofInfection and immunity · 2024
    Article
  17. Review
  18. Infection and immunity · 2024
    Article
  19. Article
  20. Frontiers in cell and developmental biology · 2024
    Review

50 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

7 authors at 4 institutions in 1 country.

Yugen ZhangDepartment of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
Laxmi YeruvaDepartment of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202;
Anthony MarinovDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA 15261;
Daniel PrantnerDepartment of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; and.
Priscilla B WyrickDepartment of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
Vladimir LupashinDepartment of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205.
Uma M NagarajanDepartment of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; nagaraja@email.unc.edu.
University of North Carolina at Chapel Hill · USUniversity of Arkansas for Medical Sciences · USUniversity of Maryland, Baltimore · USUniversity of Pittsburgh · US

Funding

Characterization of mammalian COG complex-interacting intra-Golgi trafficking macR01GM083144 · NIGMS · UNIV OF ARKANSAS FOR MED SCIS · PI VLADIMIR V LUPASHIN · 2008 to 2026
$6.5M
Molecular Mechanisms of Type I IFN Induction during Chlamydia InfectionR01AI067678 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI NAGARAJAN, UMA M · 2007 to 2018
$3.5M
NIAID NIH HHS AI067678NIAID NIH HHS R01 AI067678NIGMS NIH HHS GM083144NIGMS NIH HHS R01 GM083144
6 · The paper itself

Abstract

IFN-β has been implicated as an effector of oviduct pathology resulting from genital chlamydial infection in the mouse model. In this study, we investigated the role of cytosolic DNA and engagement of DNA sensors in IFN-β expression during chlamydial infection. We determined that three-prime repair exonuclease-1, a host 3' to 5' exonuclease, reduced IFN-β expression significantly during chlamydial infection using small interfering RNA and gene knockout fibroblasts, implicating cytosolic DNA as a ligand for this response. The DNA sensor cyclic GMP-AMP synthase (cGAS) has been shown to bind cytosolic DNA to generate cyclic GMP-AMP, which binds to the signaling adaptor stimulator of IFN genes (STING) to induce IFN-β expression. We determined that cGAS is required for IFN-β expression during chlamydial infection in multiple cell types. Interestingly, although infected cells deficient for STING or cGAS alone failed to induce IFN-β, coculture of cells depleted for either STING or cGAS rescued IFN-β expression. These data demonstrate that cyclic GMP-AMP produced in infected cGAS(+)STING(-) cells can migrate into adjacent cells via gap junctions to function in trans in cGAS(-)STING(+) cells. Furthermore, we observed cGAS localized in punctate regions on the cytosolic side of the chlamydial inclusion membrane in association with STING, indicating that chlamydial DNA is most likely recognized outside the inclusion as infection progresses. These novel findings provide evidence that cGAS-mediated DNA sensing directs IFN-β expression during Chlamydia trachomatis infection and suggest that effectors from infected cells can directly upregulate IFN-β expression in adjacent uninfected cells during in vivo infection, contributing to pathogenesis.

Indexed as

AnimalsChlamydia InfectionsChlamydia trachomatisCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseCytosolDNA, BacterialGap JunctionsGene Expression RegulationGene Knockdown TechniquesHeLa CellsHumansInterferon-betaMembrane ProteinsMiceNucleotides, CyclicNucleotidyltransferasescGAS protein, humancyclic guanosine monophosphate-adenosine monophosphateCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNA, BacterialInterferon-betaMembrane ProteinsNucleotides, CyclicNucleotidyltransferasesSTING1 protein, humanSTING Protein

Identifiers

PMID25070851
PMCPMC4212656
OpenAlexW2151070118

What OpenQuestion holds

Textmetadata
LicenceTDM
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.