Comparative gene expression profiling analysis of RNA-seq data for bovine macrophages infected with two Myocbacterium bovis strains of variable virulence and co-cultured with autologous lymphocytes.

In this study we compared the transcriptome of bovine macrophages infected with two Mycobacterium bovis strains of variable virulence, co-cultured with autologous lymphocytes. We used the highly virulent M. bovis strain called Mb04-303 and the attenuated Mb534 strain. We first observed that only the infection of bovine macrophages with the virulent strain, Mb04-303, induced in peripheral bovine mononuclear cells a powerful innate immune response capable of controlling the intracellular mycobacterial replication.By RNAseq analysis we found that infections with Mb04-303 downregulated the KEAP1-NFE2L2 pathway that encodes a transcriptional factor involved in antioxidant genes and inflammasome activation and upregulated the type 1 interferon signalling pathway, compared to the infections with the attenuated Mb534 strain. T Overall design: In this study macrophages infected with Mb04-303 showed reduced replication only when autologous lymphocyte were added to the infected macfophages, while macrophages infected with the attenuated M. bovis strain, Mb534, showed low bacterial loads in both conditions, with and without autologous lymphocytes. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different co-culturres after 24 hs post infection.