ArticleJournal of virology2008
Accelerated prion disease pathogenesis in Toll-like receptor 4 signaling-mutant mice.
Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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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
35 citing papers in PubMed, 52 citations in OpenAlex.
- Interferon-Stimulated Gene-Mediated Defense Against Prion Infection: Noncanonical Function of Oas1a.Viruses · 2026Review
- Microglia-specific NF-κB signaling is a critical regulator of prion-induced glial inflammation and neuronal loss.PLoS pathogens · 2025Article
- Innate Immune Mechanisms in the Central Nervous System.Advances in experimental medicine and biology · 2025Review
- RETRACTED: Neuroinflammatory Markers: Key Indicators in the Pathology of Neurodegenerative Diseases.Molecules (Basel, Switzerland) · 2022Review
- Distinctive Toll-like Receptors Gene Expression and Glial Response in Different Brain Regions of Natural Scrapie.International journal of molecular sciences · 2022Article
- Mice Treated Subcutaneously with Mouse LPS-Converted PrPVeterinary sciences · 2021Article
- Neuroinflammation in Prion Disease.International journal of molecular sciences · 2021Review
- Prion potentiation after life-long dormancy in mice devoid of PrP.Brain communications · 2021Article
- Microglia in Prion Diseases: Angels or Demons?International journal of molecular sciences · 2020Review
- Administration of FK506 from Late Stage of Disease Prolongs Survival of Human Prion-Inoculated Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Article
- Type I interferon protects neurons from prions in in vivo models.Brain : a journal of neurology · 2019Article
- Review
- Expression of selected genes isolated from whole blood, liver and obex in lambs with experimental classical scrapie and healthy controls, showing a systemic innate immune response at the clinical end-stage.BMC veterinary research · 2018Article
- Let's make microglia great again in neurodegenerative disorders.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
- Article
- Microglia in prion diseases.The Journal of clinical investigation · 2017Review
- Article
- Article
- Subtype and regional-specific neuroinflammation in sporadic creutzfeldt-jakob disease.Frontiers in aging neuroscience · 2014Article
- The immunobiology of prion diseases.Nature reviews. Immunology · 2013Review
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Prion diseases such as scrapie involve the accumulation of disease-specific prion protein, PrP(Sc), in the brain. Toll-like receptors (TLRs) are a family of proteins that recognize microbial constituents and are central players in host innate immune responses. The TLR9 agonist unmethylated CpG DNA was shown to prolong the scrapie incubation period in mice, suggesting that innate immune activation interferes with prion disease progression. Thus, it was predicted that ablation of TLR signaling would result in accelerated pathogenesis. C3H/HeJ (Tlr4(Lps-d)) mice, which possess a mutation in the TLR4 intracellular domain preventing TLR4 signaling, and strain-matched wild-type control (C3H/HeOuJ) mice were infected intracerebrally or intraperitoneally with various doses of scrapie inoculum. Incubation periods were significantly shortened in C3H/HeJ compared with C3H/HeOuJ mice, regardless of the route of infection or dose administered. At the clinical phase of disease, brain PrP(Sc) levels in the two strains of mice showed no significant differences by Western blotting. In addition, compared with macrophages from C3H/HeOuJ mice, those from C3H/HeJ mice were unresponsive to fibrillogenic PrP peptides (PrP residues 106 to 126 [PrP(106-126)] and PrP(118-135)) and the TLR4 agonist lipopolysaccharide but not to the TLR2 agonist zymosan, as measured by cytokine production. These data confirm that innate immune activation via TLR signaling interferes with scrapie infection. Furthermore, the results also suggest that the scrapie pathogen, or a component(s) thereof, is capable of stimulating an innate immune response that is active in the central nervous system, since C3H/HeJ mice, which lack the response, exhibit shortened incubation periods following both intraperitoneal and intracerebral infections.
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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.