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Evidence of Microglial Immune Response Following Coronavirus PHEV Infection of CNS
Jing Zhang1, Zi Li1, Huijun Lu2
1Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.
Abstract:
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic coronavirus that invades the host central nervous system (CNS) and causes neurological dysfunction. Microglia are key immune cells in the CNS, however, whether and how they response to PHEV infection remains unclear. Herein, microglial activation and proliferation were detected in the CNS of PHEV-infected mice, as along with the proinflammatory response. Moreover, the production of proinflammatory cytokines induced by moderately activated microglia limited viral replication in the early stage of infection. Microglial depletion assays showed that during late infection, excess activation of microglia aggravated neurological symptoms, BBB destruction, and peripheral monocyte/macrophage infiltration into the CNS. Using an in vitro brain slice model, PHEV was identified to specifically and moderately induce microglial activation in the absence of peripheral immune cells infiltration. Consistently, macrophage clearance from circulating blood indicated that peripheral monocytes/macrophages crossing the BBB of mice were responsible for excess activation of microglia and CNS damage in late PHEV infection. Overall, our findings provide evidence supporting a dual role for microglia in the host CNS in response to coronavirus PHEV invasion.
Insights
Porcine hemagglutinating encephalomyelitis virus (PHEV) infection causes dual effects from microglia: early immune response limits virus, while late overactivation worsens neurological damage and BBB breakdown.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Porcine hemagglutinating encephalomyelitis virus (PHEV) is a neurotropic coronavirus.
- PHEV infection leads to central nervous system (CNS) dysfunction.
- The role of microglia in PHEV infection is not well understood.
Purpose of the Study:
- To investigate microglial activation and their role in PHEV-induced CNS disease.
- To elucidate the dual function of microglia during different stages of PHEV infection.
Main Methods:
- Studied microglial activation and proliferation in PHEV-infected mouse CNS.
- Utilized microglial depletion assays to assess their impact.
- Employed an in vitro brain slice model to study PHEV-induced microglial response.
- Monitored peripheral monocyte/macrophage infiltration and blood-brain barrier (BBB) integrity.
Main Results:
- PHEV infection induced microglial activation, proliferation, and a proinflammatory response in the CNS.
- Moderate microglial activation initially limited PHEV replication.
- Excessive microglial activation during late infection exacerbated neurological symptoms, BBB damage, and immune cell infiltration.
- In vitro models confirmed PHEV specifically induces moderate microglial activation without peripheral immune cells.
- Peripheral monocytes/macrophages infiltrating the CNS contributed to late-stage damage.
Conclusions:
- Microglia play a dual role in PHEV infection, exhibiting both protective and detrimental effects.
- Early microglial activation aids in controlling viral replication.
- Late-stage excessive microglial activation and peripheral immune cell infiltration worsen CNS pathology in PHEV infection.
