Our laboratory seeks to understand how innate immune programs control central nervous system responses to viral infections and autoimmune inflammation. A major goal is to elucidate cellular and molecular mechanism that allow regional, context-dependent, and differential responses of glia to direct the functions of infiltrating and resident T cells. We utilize multiple viral and autoimmune models and a broad array of approaches that range from single cell analyses to multiphoton intravital imaging to identify fundamental processes that behavior consistently across different diseases.
This video shows a 3D reconstruction from confocal Z‐stack images of immunostaining of CX3CR1‐GFP and the presynaptic marker, synaptophysin, in CX3CR1‐GFP +/‐ mice in hippocampus of WNV‐NS5‐E218A‐infected mouse at day 7 post‐infection. Vasek et al. shows that complement C3 and C3aR mediate presynaptic terminal loss in the hippocampi of mice that exhibit spatial learning defects during recovery from West Nile virus disease, and that microglia and recognition of C3 cleavage products by complement receptor C3aR are required for this process (Nature, 2016).This video shows a 3D reconstruction from confocal Z-stack images of immunostaining of the neural cell body marker, NeuN, and the microglia marker, IBA1, in hippocampus of ZIKV-infected mouse at day 25 post-infection. Garber and Soung et al. found that Zika virus preferentially targets and induces the loss of neurons throughout the hippocampus, which was also associated with the loss of postsynaptic Homer1+ termini, and that microglia may be critically involved in responses to T cell-derived IFN-γ that drive this process and subsequent cognitive impairment after infection ZIKV (Nature Neuroscience, 2019).