Unique gene expression profiles of microglia and astrocytes following innate immune activation

Both astrocytes and microglia are often activated in association with diseases of the central nervous system (CNS), including virus-induced neurological disease. Understanding how activation alters the transcriptome of these cells may offer valuable insight in regards to how activated cells mediate neurological damage. Furthermore, identifying common and unique pathways of gene expression during activation may provide new insight into the distinct roles these cells have in the CNS during infection and inflammation. In the current study, we utilized microarray analysis to examine the response of astrocyte and microglia to specific innate immune stimuli. Since virus infections often induce activation of toll-like receptor 7 (TLR7), we used the TLR7 agonist imiquimod that has been shown to induce activation of both microglia and astrocytes in vivo and in vitro. We found that microglia generate a much stronger response to TLR7 activation than astrocytes, with the upregulation and downregulation of substantially more genes in microglia than that observed in astrocytes. We identified genes that were uniquely upregulated by each cell type and examined these genes for upregulation by other factors including virus infection. These data provide new insights into innate immune activation of astrocytes and microglia that will be useful in characterizing the cellular responses of these genes during infection or insult of the CNS.