Microglia are the only resident myeloid cells in the central nervous system (CNS) parenchyma, but the role of microglia in the context of neurotropic viral infection is poorly understood. This work aims to define the role of microglia in acute and chronic neurotropic picornavirus infection. 

Viral encephalitis is estimated to affect approximately 4 people per 100,000 per year. Microglia are professional antigen presenting cells that are capable of crosstalk with T cells to coordinate the antiviral response. However, microglia also express inflammatory effectors that can contribute to neuropathology. Parsing critical antiviral functions versus neuropathological functions of microglia will be important to improve interventions for viral encephalitis.

Using Theiler’s murine encephalomyelitis virus (TMEV) in acute and chronic neurotropic infection models and PLX5622, a colony stimulating factor-1 receptor inhibitor that selectively depletes microglia in the CNS, we probed the contribution of microglia to the CNS antiviral response.

We find that microglia depletion in an acute infection model results in fatal encephalitis with low titer TMEV infection that is sub-lethal in microglia-competent animals. These mice have no hinderance of immune cell infiltration into the CNS, however, the expression of antigen presentation machinery was decreased in myeloid cells and CD4+ T cells were less activated. Surprisingly, microglia depletion in chronic TMEV infection does not result in fatal encephalitis, but exacerbates paralysis associated with TMEV-induced demyelination. Microglia-depleted mice exhibit deficits in T cell infiltration in chronically infected mice, however the effect of microglia depletion can be ameliorated by reconstituting the microglia niche.

Our results suggest that microglia are major orchestrators of the CNS antiviral response. In acute infection, microglia are important to support the antigen presentation function of infiltrating myeloid cells and the activation of CD4+ T cells. In chronic infection, microglia appear to be necessary for proper infiltration of T cells into the CNS.