Role of the DNA sensors cGAS and ZBP1 in DNA damage and viral infections in glia

Resident CNS cells, such as astrocytes and microglia, are known to produce critical immune mediators following CNS infection due to the recognition of pathogen and damage-associated molecular patterns by specialized pattern recognition receptors (PRRs). Recently, multiple intracellular PRRs, including cyclic GMP-AMP synthase (cGAS), interferon gamma-inducible 16 (IFI16), absent in melanoma 2 (AIM2), and Z-DNA binding protein 1 (ZBP1), have been identified as cytosolic DNA sensors and play critical roles in glial immune responses to infectious agents. Intriguingly, some nucleic acid sensors have recently been shown to recognize endogenous DNA resulting from DNA damage and subsequently trigger immune responses in peripheral cell types, however, in the CNS, our understanding of these responses are limited. In this dissertation, we describe the functionality of the DNA sensors ZBP1, with regards to herpes simplex virus type-1 (HSV-1) infection in murine astrocytes and microglia, and cGAS with regards to DNA damage in human microglia.