Modifications in the Gene Expression of Microglia Following Peripheral Mycobacterium Challenge

Communication between the immune system and the brain is implicated in the psychological pathologies associated with immunological alterations. An experiment was conducted to elucidate the transcriptomic changes in the microglia, the cells that mediate the brains immune response, associated with an immune challenge. Male adult mice (C57BL/6J, ~22 weeks; n=2/group) were systemically (intraperitoneal) challenged with Bacille Calmette-Guérin (BCG; 10 mg) or physiological saline (Control). For each mouse, microglia were enzymatically isolated 7 d post-challenge and RNA extracted from each microglia sample. Paired-end reads were obtained using Illumina HiSeq 2000 and mapped to the mouse reference genome (GRCm38) using Tophat. Differential expression of 29,873 transcripts between BCG and Control groups was tested using Cufflinks. Among these, 109 genes exhibited differential expression (FDR-adjusted p-value < 0.05). Top genes over-expressed in BCG relative to Control included: complement component 3 (C3), guanylate binding protein 2 (Gbp2), interferon induced transmembrane protein 1 (Ifitm1) and Lymphocyte antigen 6 complex, locus A (Ly6a). These results are consistent with prior studies of the microglial transcriptome in immune-activated states. Six functional category clusters were enriched (DAVID Enrichment Score > 2) among the significantly differentially expressed genes. Clusters included: enzyme inhibitor activities, defensive and bacterial immune responses, and carbohydrate binding. These categories suggest a spectrum of transcriptome changes in the microglia after systemic immune challenge that could help understanding the psychological responses.