Bacterial and viral pathogen associated molecular patterns create different early transcriptomic landscapes in bovine macrophages

Abstract

Pathogens stimulate immune functions of dendritic cells and macrophages (MΦ). There is no clear understanding of the nature of transcriptomic changes caused in cells upon stimulation through pattern recognition receptors by various pathogens. Our study investigated the early transcriptomic changes of bovine MΦ in response to stimulation with CpG or poly I:C. BMΦ were incubated with CpG or pI:C for 6 h and RNA isolated for transcriptomic analysis by RNAseq. Bioinformatics tools were used to analyze differentially expressed genes (DE). Results showed that, of the 13740 genes mapped to the bovine genome, 2245 had p-value ≤0.05, deemed as DE. At 6 h post stimulation, pI:C induced a different transcriptomic profile from that induced by CpG. CpG upregulated 347 and downregulated 210 genes. pI:C upregulated 761 and downregulated 414 genes. The highest expressed genes in both stimulations belonged to the TNF superfamily, TNFSF18 (CpG) and TNFSF10 (pI:C) and in both cases the lowest downregulated gene was CYP1A1. CpG induced canonical pathways that are unrelated to immune response in BMΦ in contrast to pI:C which induced canonical pathways directly related to antiviral immune functions dominated by IFN signalling genes. The transcriptomic profile after pI:C stimulation was consistent with TLR3 signalling. CpG influenced expression of genes involved in molecular and cellular functions in free radical scavenging. We conclude that CpG and pI:C induce different early transcriptional landscapes in BMΦ line, but each suited to a specific function of BMΦ during interaction with pathogens.