West Nile virus (WNV) is a neuroinvasive mosquito borne pathogen endemic to many parts of the world. Although infection is typically asymptomatic or causes minor illness, some individuals develop severe and potentially lethal encephalitis with a significant immunopathological component. Currently, only supportive treatment is available, and therefore research to increase understanding of disease and development of treatments is critical.
We specifically study the immune response to WNV in the CNS in an intranasal mouse model of infection and have detailed a large influx of leukocytes from day 6 p.i. Targeting and diverting CNS infiltrating Ly6C+ inflammatory monocytes to the spleen with novel therapeutic, immune-modifying microparticles (IMP), results in survival in up to 70% of WNV-infected mice that would otherwise succumb to disease1. Several leukocyte populations, including CD4+ T cells, CD8+ T cells and NK cells, also traffic to the brain in significant numbers during infection, but their role remains unclear. However, their precise role is of great interest as viral clearance from the CNS is achieved in absence of Ly6C+ inflammatory monocytes and the associated immune pathological damage. Therefore we aim to determine the part these individual leukocyte subsets play in WNV encephalitis by combining IMP treatment with depletion of specific leukocyte subsets using monoclonal antibodies, working towards a multi-targeted approach. We found that CD4+ T cell depletion in conjunction with IMP therapy results in increased clinical severity, reduction of survival by 25% and increased viral titres in the brain, suggesting an important role for these cells in viral clearance following IMP treatment. Depletion of NK cells suggests a less important role in resolving infection. The role of CD4+ T cells, CD8+ T cells and NK cells in resolving infection and the specific characterization of beneficial and detrimental subsets, requires further investigation and may lead to their modulation in a therapeutic scenario.