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and protein analysis to identify the unique profiles of microglia and astrocytes in their response to PRR signaling (unpublished observations).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, 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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Gershburg, Svetlana; Geltz, Joshua; Peterson, Karin E et al. (2015) The UL13 and US3 Protein Kinases of Herpes Simplex Virus 1 Cooperate to Promote the Assembly and Release of Mature, Infectious Virions. PLoS One 10:e0131420
Madeddu, Silvia; Woods, Tyson A; Mukherjee, Piyali et al. (2015) Identification of Glial Activation Markers by Comparison of Transcriptome Changes between Astrocytes and Microglia following Innate Immune Stimulation. PLoS One 10:e0127336
Winkler, Clayton W; Taylor, Katherine G; Peterson, Karin E (2014) Location is everything: let-7b microRNA and TLR7 signaling results in a painful TRP. Sci Signal 7:pe14
Grasperge, Britton J; Morgan, Timothy W; Paddock, Christopher D et al. (2014) Feeding by Amblyomma maculatum (Acari: Ixodidae) enhances Rickettsia parkeri (Rickettsiales: Rickettsiaceae) infection in the skin. J Med Entomol 51:855-63
Christensen, Leah B; Woods, Tyson A; Carmody, Aaron B et al. (2014) Age-related differences in neuroinflammatory responses associated with a distinct profile of regulatory markers on neonatal microglia. J Neuroinflammation 11:70
Evans, Leonard H; Boi, Stefano; Malik, Frank et al. (2014) Analysis of two monoclonal antibodies reactive with envelope proteins of murine retroviruses: one pan specific antibody and one specific for Moloney leukemia virus. J Virol Methods 200:47-53
Snook, Eric R; Fisher-Perkins, Jeanne M; Sansing, Hope A et al. (2014) Innate immune activation in the pathogenesis of a murine model of globoid cell leukodystrophy. Am J Pathol 184:382-96
Baker, David G; Woods, Tyson A; Butchi, Niranjan B et al. (2013) Toll-like receptor 7 suppresses virus replication in neurons but does not affect viral pathogenesis in a mouse model of Langat virus infection. J Gen Virol 94:336-47
Lopez, Job E; Wilder, Hannah K; Hargrove, Reid et al. (2013) Development of genetic system to inactivate a Borrelia turicatae surface protein selectively produced within the salivary glands of the arthropod vector. PLoS Negl Trop Dis 7:e2514
Du, Min; Butchi, Niranjan B; Woods, Tyson et al. (2011) Poly-thymidine oligonucleotides mediate activation of murine glial cells primarily through TLR7, not TLR8. PLoS One 6:e22454

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