Neuroinflammatory responses may be dependent on the initiation of innate immune responses triggered by the stimulation of intrinsic brain cells by pathogen-associated molecular patterns (PAMPs), repeated structural motifs generated by microbes that are not normally found in the host or by debris from apoptotic or necrotic cells following injury. However, there is a lack of basic understanding of which cell types in the brain respond to stimulation of PRRs, as well as the pathways of neuroinflammation, neuroprotection and/or neuronal damage induced when these PRRs are activated on different cell types. Understanding the mechanism of PRR-induced activation of different cell types in the CNS is important for understanding viral pathogenesis as well as identifying potential pathways for therapeutic treatments. Our laboratory has focused on understanding the response of intrinsic brain cells following PRR activation or during virus infection and determining the downstream effects of innate immune activation on neuroinflammation and neuropathogenesis. In FY2013, we utilized microarray, real-time PCR and protein analysis to identify the unique profiles of microglia and astrocytes in their response to PRR signaling (unpublished observations). We also analyzed the specific role of toll-like receptors and RLRs during virus infection in the CNS using different virus infection models. One of the major discoveries was the important role for TLR7 in controlling virus infection in neurons. Interestingly, TLR7 was shown to negatively regulate type I IFN responses to virus infection in neurons (Baker, et.al.). Additional studies are directed at analyzing the role of neuropeptide Y (NPY) produced by neurons in regulating monocyte/macrophage influx into the CNS during retrovirus infection.
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