RNA sequencing demonstrates large-scale temporal dysregulation of gene expression in stimulated macrophages derived from MHC-defined chicken haplotypes

Abstract

Discovering genetic biomarkers associated with disease resistance and enhanced immunity is critical to developing advanced strategies for controlling viral and bacterial infections in different species. Macrophages, important cells of innate immunity, are directly involved in cellular interactions with pathogens, the release of cytokines activating other immune cells and antigen presentation to cells of the adaptive immune response. IFNγ is a potent activator of macrophages and increased production has been associated with disease resistance in several species. This study characterizes the molecular basis for dramatically different nitric oxide production and immune function between the B2 and the B19 haplotype chicken macrophages.A large-scale RNA sequencing approach was employed to sequence the RNA of purified macrophages from each haplotype group (B2 vs. B19) during differentiation and after stimulation. Our results demonstrate that a large number of genes exhibit divergent expression between B2 and B19 haplotype cells both prior and after stimulation. These differences in gene expression appear to be regulated by complex epigenetic mechanisms that need further investigation.

Genetic variation in chicken interferon signalling pathway genes in research lines showing differential viral resistance

“…Using miRDB, it was seen that potential miRNA binding sites for gga-miR-1627-3p and gga-miR-196-1-3p in the 3′UTR of IFNAR1 were altered by SNPs at positions Chr1:106632281 and Chr1:106631586 respectively. Gga-miR-1627-3p was previously found to exhibit greater expression in macrophages with the MHC haplotype B19 compared with those with B2, suggesting that it may play a role in immune response (Irizarry et al, 2017). The SNP affecting the gga-miR-1627-3p binding site only occurs in line 0, which is perceived as resistant to AIV, so it is therefore plausible that this SNP could contribute to this resistant phenotype.…”