The Brain Has an Innate Immune Response That Can Limit Virus Spread

The brain has a tightly regulated environment that protects non-regenerating post-mitotic neurons and limits inflammation, which led to its description as a site of ‘immune privilege’. For example, viral and bacterial stimuli elicit a weaker immune response within the brain than following systemic application; injection of pathogenic stimuli into the brain leads to significantly less, if any, monocyte recruitment, T-cell priming and B-cell antibody production when compared to systemic applications over the same time period. However, the difference between the immune response of the brain and systemic circulation is not absolute, but rather relative, and applies to both the innate and adaptive immune systems. Innate immunity provides a rapid response to infections, which is often referred to as a first line of host defense, and it also enhances adaptive immune responses. Innate immune pathways are activated in the brain by local infections, during neurodegeneration, as part of neuropsychiatric disorders, and following systemic pathogenic stimuli. However, the types of innate immune pathways that are activated in the brain are unclear, including the types of cells that mount an innate immune response, and the ways in which particular cell types respond to the different innate immunity signaling molecules are also not well defined. Perhaps of most importance, however, is whether these responses are functionally effective and can limit virus spread in the brain. The brain is structurally complex, harboring extensive interactions with both the lymphatic and vascular architecture. Within the brain, the parenchyma, which includes the white and grey matter, is the area of immune privilege. We sought to test if the brain parenchyma has the cellular and molecular elements to initiate an innate immune response capable of limiting the spread of directly delivered virus. We injected VSV, a well-characterized transsynaptic tracer, or VSV-derived defective interfering particles, into the caudate-putamen and scored for an innate immune response and inhibition of virus spread. We report that the brain parenchyma has a functional type I interferon response that can limit VSV spread at both the inoculation site and between neurons. Furthermore, we characterize the response of the microglia, which are believed to be the brain’s immune cells, to VSV infection and demonstrate that infected microglia produce type I interferon and that the innate immune response is induced in un-infected microglia following infection.Medical Science