RIPK3 promotes brain region-specific interferon signaling and restriction of tick-borne flavivirus infection.

Interactions between the nervous and immune systems are very carefully orchestrated in order to protect the brain and spinal cord from immune-mediated damage, while still maintaining protective defenses against infection. These specialized neuro-immune interactions have been shown to vary significantly across regions of the brain, with innate antiviral signaling being particularly strong in the cerebellum, although the reasons for this are poorly understood. Here, we show a specialized adaptation of programmed cell death signaling that uniquely protects the cerebellum from tick-borne flavivirus infection. These findings provide important new insight into the molecular mechanisms that promote the uniquely robust antiviral immunity of the cerebellum. They also provide new clues into the pathogenesis of tick-borne encephalitis, a zoonosis of significant global concern.