Microglia have a protective role in viral encephalitis-induced seizure development and hippocampal damage

Brain Behav Immun. 2018 Nov;74:186-204. doi: 10.1016/j.bbi.2018.09.006. Epub 2018 Sep 11.

Abstract

In the central nervous system (CNS), innate immune surveillance is mainly coordinated by microglia. These CNS resident myeloid cells are assumed to help orchestrate the immune response against infections of the brain. However, their specific role in this process and their interactions with CNS infiltrating immune cells, such as blood-borne monocytes and T cells are only incompletely understood. The recent development of PLX5622, a specific inhibitor of colony-stimulating factor 1 receptor that depletes microglia, allows studying the role of microglia in conditions of brain injury such as viral encephalitis, the most common form of brain infection. Here we used this inhibitor in a model of viral infection-induced epilepsy, in which C57BL/6 mice are infected by a picornavirus (Theiler's murine encephalomyelitis virus) and display seizures and hippocampal damage. Our results show that microglia are required early after infection to limit virus distribution and persistence, most likely by modulating T cell activation. Microglia depletion accelerated the occurrence of seizures, exacerbated hippocampal damage, and led to neurodegeneration in the spinal cord, which is normally not observed in this mouse strain. This study enhances our understanding of the role of microglia in viral encephalitis and adds to the concept of microglia-T cell crosstalk.

Keywords: Hippocampus; Monocytes; Neuroinflammation; Seizures; Spinal cord; T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / immunology
  • Central Nervous System / immunology
  • Disease Models, Animal
  • Encephalitis / immunology
  • Encephalitis, Viral / immunology
  • Encephalitis, Viral / virology
  • Epilepsy / physiopathology
  • Female
  • Hippocampus / immunology
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Microglia / immunology*
  • Microglia / physiology*
  • Monocytes / immunology
  • Organic Chemicals / pharmacology
  • Seizures / physiopathology*
  • Theilovirus / immunology

Substances

  • Organic Chemicals
  • PLX5622