Microglia from Creutzfeldt-Jakob disease-infected brains are infectious and show specific mRNA activation profiles
Open accessAbstract
Neurons are often assumed to be the principal sites for replication of the infectious agents causing Creutzfeldt-Jakob disease (CJD), scrapie, and bovine spongiform encephalopathy because they express high levels of normal and pathological prion protein (PrP). However, isolated brain cell types have not been evaluated for either infection or gene expression. Microglia purified from CJD-infected mice showed infectivity comparable to that of starting brain homogenate but expressed ∼50-fold less PrP. CJD-infected microglia also displayed morphological changes indicative of cellular activation. To determine the molecular pathways of activation, we evaluated pertinent transcripts, including those linked to inflammation. Semiquantitative reverse transcription-PCR showed a >4-fold increase in cathepsin S, an enzyme important in antigen presentation, the cytokine interleukin-1β, and the chemokine B-lymphocyte chemoattractant. The profile of microglial changes induced by the CJD agent differed substantially from activation induced by bacterial lipopolysaccharide or by β-amyloid, a structure comparable to pathological PrP. These microglial studies emphasize migratory hematopoietic cells in the dispersion, and possibly replication, of the CJD agent. The low PrP levels in these highly infectious and activated cells further support the concept that pathological PrP is the result of infection rather than the infectious agent itself. Because microglia develop a specific pattern of responses to the CJD agent, microglial markers may be exploited in the diagnosis of these spongiform encephalopathies.
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Microglia isolated from the brains of prion-infected mice are infectious.
“This is in line with findings showing that microglia isolated from the brains of prion-infected mice are infectious [58].”
From Loss of Homeostatic Microglia Signature in Prion Diseases (2022) · cites this paper as [58]
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“This is in line with findings showing that microglia isolated from the brains of prion-infected mice are infectious [58].”
Result
- Authors
- Baker, C. A., Martin, D., & Manuelidis, L.
- Affiliations
- Yale University (US)
- Corresponding author
- Manuelidis, Laura
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2002-11
- Volume
- 76
- Issue
- 21
- Pages
- 10905-10913
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC136595
- OpenAlex
- W2146631683
- Cited by
- 128
- References
- 48
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 3 · 2017: 8 · 2016: 7 · 2015: 4 · 2014: 1 · 2013: 6 · 2012: 7
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01ns034569-15)
- National Institute of Neurological Disorders and Stroke (R01NS012674, R56NS012674, NS34569, NS12674)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Creutzfeldt-Jakob disease, prion disease, microglia, prion protein, prion infection, microglial activation, cathepsin S, IL-1β, amyloid-beta, spongiform encephalopathy, scrapie, bovine spongiform encephalopathy, neuroinflammation, prion replication, microglial markers
- MeSH terms
- CD68 Molecule, Animals, Brain, Interleukin-1, Creutzfeldt-Jakob Syndrome, Lipopolysaccharides, RNA, Messenger, Tumor Necrosis Factor-alpha, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Gene Expression, Receptor, Macrophage Colony-Stimulating Factor, Amyloid beta-Peptides, Leukocyte Common Antigens, Microglia, CD40 Antigens, Receptors, CCR5, Chemokines, CXC, Gene Expression Profiling, Mice, Chemokine CXCL10
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