MyD88 signaling by neurons induces chemokines that recruit protective leukocytes to the virus-infected CNS

Viral encephalitis initiates a series of immunological events in the brain that can lead to brain damage and death. Astrocytes express IFN-beta in response to neurotropic infection, whereas activated microglia produce proinflammatory cytokines and accumulate at sites of infection. Here, we observed that neurotropic vesicular stomatitis virus (VSV) infection causes recruitment of leukocytes into the central nervous system (CNS), which requires MyD88, an adaptor of Toll-like receptor and interleukin-1 receptor signaling. Infiltrating leukocytes, and in particular CD8(+) T cells, protected against lethal VSV infection of the CNS. Reconstitution of MyD88, specifically in neurons, restored chemokine production in the olfactory bulb as well as leukocyte recruitment into the infected CNS and enhanced survival. Comparative analysis of the translatome of neurons and astrocytes verified neurons as the critical source of chemokines, which regulated leukocyte infiltration of the infected brain and affected survival.

Automated summary

Viral encephalitis triggers a series of immunological events in the brain that can result in brain damage and death. The recruitment of leukocytes into the CNS after neurotropic infection is dependent on MyD88, with infiltrating CD8(+) T cells playing a protective role against lethal CNS VSV infection. Neurons are identified as a critical source of chemokines that regulate leukocyte infiltration in the infected brain and impact survival.