Microglia have a more extensive and divergent response to interferon-alpha compared with astrocytes

ABSTRACT: Type I interferons (IFN-I) are crucial for effective antimicrobial defence in the central nervous system (CNS) but also can cause severe neurological disease (termed cerebral interferonopathy) as exemplified by Aicardi-Goutières Syndrome and chronic viral infection. In the CNS, microglia and astrocytes have essential roles in host responses to infection and injury, with both cell types responding to IFN-I. However, the extent to which the IFN-I responses of these cells differ, if at all, is still unknown. Here we determined the global transcriptional responses of astrocytes and microglia to the IFN-I, IFN-alpha. MGCs were prepared from 2–4 day-old C57BL/6 mice. Purified primary astrocytes were obtained from the MGCs by magnetic activated cell sorting using anti-CD11b beads. Microglia were obtained from mixed glial cell cultures by mechanical shaking for 4 h. After treating astrocytes and microglia with IFN-alpha for 12 h, microarray using Affymetrix mouse genome array 430 2.0 array was performed on total RNA extracted from these cells. We found that under basal conditions, each cell type has a unique gene expression pattern reflective of its developmental origin and biological function. Following stimulation with IFN-alpha for 12 h, astrocytes and microglia also displayed a common core response that was characterized by the increased expression of genes required for pathogen detection and elimination. Microglia had a more extensive and diverse response to IFN-alpha with twice the number of genes upregulated (282 vs. 141 genes) when compared with astrocytes. Validation of the findings in vivo further suggested that astrocytes and microglia play important but distinct roles in the development of IFN-alpha-driven cerebral interferonopathies.

ORGANISM(S): Mus musculus

SUBMITTER: Wen Li 

PROVIDER: E-MTAB-6301 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress