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Microglia have limited influence on early prion pathogenesis, clearance, or replication
Brent Race1, Katie Williams1, Chase Baune1
1Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
Plos One
|October 27, 2022
Summary
Microglia (MG) do not appear to protect against early prion disease. Reducing MG in mice did not increase susceptibility or alter prion clearance and replication in initial infection stages.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Microglia (MG) are key immune cells in the brain, crucial for host defense, but their role in prion infection neuroprotection is unclear.
- Understanding MG influence is vital for developing therapeutic strategies against prion diseases.
Purpose of the Study:
- To investigate the role of microglia in early prion pathogenesis, clearance, and replication.
- To assess the impact of microglia depletion on prion infection susceptibility and disease progression.
Main Methods:
- Used PLX5622 to reduce microglia in C57BL/10 and tga20 mouse models.
- Assessed prion clearance and replication via bioassay, immunohistochemistry, and RT-QuIC.
- Investigated intermittent microglia reduction and repopulation strategies.
Main Results:
- Microglia were excluded from the inoculation site early in C57BL/10 mice; infiltrating monocytes/macrophages were present.
- Reducing microglia did not increase susceptibility to prion infection.
- Intermittent microglia reduction and depletion in tga20 mice showed minimal impact on prion pathogenesis.
Conclusions:
- Microglia do not appear to play a significant role in early prion pathogenesis, clearance, or replication.
- The protective role of microglia against prion disease may be more relevant in later disease stages.
