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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglia play an important role in PRV infection-induced immune responses of the central nervous system
Xiuxiu Sun1, Xinxin Jin1, Xi Liu1
1Division of Veterinary Pathology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Abstract:
Pseudorabies virus (PRV) can infect multiple hosts and lead to fatal encephalitis. There is a significant increase in the number of microglia in the brain of animals infected with PRV. However, whether and how microglia contribute to central nervous system damage in PRV infection remain unknown. In the present study, we elucidated that PRV infection can cause more severe inflammatory cell infiltration, thicker and more numerous vessel sleeve walls, and more severe inflammatory responses in the brains of natural hosts (pigs) than in those of nonnatural hosts (mice). In a mice infection model, activated microglia restricted viral replication in the early stage of infection. Acute neuroinflammation caused by microglia hyperactivation at late-stage of infection. Furthermore, in vitro experiments revealed that microglia restricted viral replication and decreased viral infectivity. This may be associated with the phagocytic ability of microglia because we observed a significant increase in the expression of the membrane receptor TREM2 in microglia, which is closely related to phagocytosis, we observed that depletion of microglia exacerbated neurological symptoms, blood-brain barrier breakdown, and peripheral lymphocyte infiltration. Taken together, we revealed the dual role of microglia in protecting the host and neurons from PRV infection.
Insights
Microglia play a dual role in Pseudorabies virus (PRV) infection. Initially, they restrict viral replication, but later, hyperactivated microglia contribute to neuroinflammation and brain damage.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Pseudorabies virus (PRV) causes fatal encephalitis and increases brain microglia.
- The specific role of microglia in PRV-induced central nervous system damage is not well understood.
Purpose of the Study:
- To elucidate the role of microglia in Pseudorabies virus infection and its impact on the central nervous system.
Main Methods:
- Comparative analysis of PRV infection in natural (pigs) and non-natural (mice) hosts.
- Infection models in mice to study microglia activation and function.
- In vitro experiments to assess microglia's effect on viral replication and infectivity.
- Analysis of TREM2 expression in microglia.
Main Results:
- PRV infection induced more severe inflammation and neuropathology in pigs than in mice.
- Activated microglia initially restricted PRV replication but led to hyperactivation and neuroinflammation late in infection.
- Microglia restricted viral replication and infectivity in vitro, associated with increased TREM2 expression.
- Microglia depletion worsened neurological symptoms, blood-brain barrier disruption, and lymphocyte infiltration.
Conclusions:
- Microglia exhibit a dual role in PRV infection, offering protection in early stages and contributing to pathology in later stages.
- Microglia's phagocytic activity, potentially mediated by TREM2, is crucial for controlling PRV.
- Targeting microglia may offer therapeutic strategies for PRV-induced encephalitis.
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