ArticlePLoS pathogens2013
The protein kinase double-stranded RNA-dependent (PKR) enhances protection against disease cause by a non-viral pathogen.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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.
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.
Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Mutual regulations betweenFrontiers in immunology · 2024Review
- Autophagy in protists and their hosts: When, how and why?Autophagy reports · 2023Article
- Toll-Like Receptor 3 (TLR3) Is Engaged in the Intracellular Survival of the Protozoan ParasiteInfection and immunity · 2022Article
- The role of PKC/PKR in aging, Alzheimer's disease, and perioperative neurocognitive disorders.Frontiers in aging neuroscience · 2022Article
- Impact of IFN-y and CD40 signalling on Toxoplasma gondii cyst formation in differentiated Neuro-2a neuroblastoma cells.Parasite immunology · 2022Article
- Lessons from Toxoplasma: Host responses that mediate parasite control and the microbial effectors that subvert them.The Journal of experimental medicine · 2021Review
- Recent Advances in the Roles of Autophagy and Autophagy Proteins in Host Cells DuringFrontiers in cell and developmental biology · 2021Review
- Protein Kinase R in Bacterial Infections: Friend or Foe?Frontiers in immunology · 2021Review
- Hiding in Plain Sight: Formation and Function of Stress Granules During Microbial Infection of Mammalian Cells.Frontiers in molecular biosciences · 2021Review
- Protein Kinase R Restricts the Intracellular Survival ofFrontiers in microbiology · 2020Article
- Toxoplasma gondii induces prolonged host epidermal growth factor receptor signalling to prevent parasite elimination by autophagy: Perspectives for in vivo control of the parasite.Cellular microbiology · 2019Article
- Amazonian Phlebovirus (Bunyaviridae) potentiates the infection of Leishmania (Leishmania) amazonensis: Role of the PKR/IFN1/IL-10 axis.PLoS neglected tropical diseases · 2019Article
- Interplay BetweenFrontiers in cellular and infection microbiology · 2019Review
- Downregulated apoptosis and autophagy after anti-Aβ immunotherapy in Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2018Observational
- PCR array profiling of antiviral genes in human embryonic kidney cells expressing human coronavirus OC43 structural and accessory proteins.Archives of virology · 2018Article
- Toxoplasma gondii induces FAK-Src-STAT3 signaling during infection of host cells that prevents parasite targeting by autophagy.PLoS pathogens · 2017Article
- Systems Approach Reveals Nuclear Factor Erythroid 2-Related Factor 2/Protein Kinase R Crosstalk in Human Cutaneous Leishmaniasis.Frontiers in immunology · 2017Article
- Identification of Signaling Pathways by Which CD40 Stimulates Autophagy and Antimicrobial Activity against Toxoplasma gondii in Macrophages.Infection and immunity · 2016Article
- HIV-1 Tat protein enhances the intracellular growth of Leishmania amazonensis via the ds-RNA induced protein PKR.Scientific reports · 2015Article
- PKR deficiency alters E. coli-induced sickness behaviors but does not exacerbate neuroimmune responses or bacterial load.Journal of neuroinflammation · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
PKR is well characterized for its function in antiviral immunity. Using Toxoplasma gondii, we examined if PKR promotes resistance to disease caused by a non-viral pathogen. PKR(-/-) mice infected with T. gondii exhibited higher parasite load and worsened histopathology in the eye and brain compared to wild-type controls. Susceptibility to toxoplasmosis was not due to defective expression of IFN-γ, TNF-α, NOS2 or IL-6 in the retina and brain, differences in IL-10 expression in these organs or to impaired induction of T. gondii-reactive T cells. While macrophages/microglia with defective PKR signaling exhibited unimpaired anti-T. gondii activity in response to IFN-γ/TNF-α, these cells were unable to kill the parasite in response to CD40 stimulation. The TRAF6 binding site of CD40, but not the TRAF2,3 binding sites, was required for PKR phosphorylation in response to CD40 ligation in macrophages. TRAF6 co-immunoprecipitated with PKR upon CD40 ligation. TRAF6-PKR interaction appeared to be indirect, since TRAF6 co-immunoprecipitated with TRAF2 and TRAF2 co-immunoprecipitated with PKR, and deficiency of TRAF2 inhibited TRAF6-PKR co-immunoprecipitation as well as PKR phosphorylation induced by CD40 ligation. PKR was required for stimulation of autophagy, accumulation the autophagy molecule LC3 around the parasite, vacuole-lysosomal fusion and killing of T. gondii in CD40-activated macrophages and microglia. Thus, our findings identified PKR as a mediator of anti-microbial activity and promoter of protection against disease caused by a non-viral pathogen, revealed that PKR is activated by CD40 via TRAF6 and TRAF2, and positioned PKR as a link between CD40-TRAF signaling and stimulation of the autophagy pathway.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.