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.
Highlights
The B19 cells show differences in 386 genes during this same period, but interestingly, 356 of these genes exhibit decreased expression during this same time interval. These results suggest that a global disruption of temporal gene expression underlies the observed differences in differentiation, activation and nitric oxide production from macrophages derived from the two different major histocompatibility complex (MHC) haplotypes
We have tried to elucidate possible mechanisms involved in enhanced disease resistance and macrophage functions displayed by B2 haplotype chickens compared to B19
This study highlights the complex gene expression patterns involved in macrophage differentiation and activation
Summary
Animal protocols were performed under the approval of the Institutional Animal Care and Use Committee at Western University of Health Sciences, Pomona, California (WesternU). Fertilized eggs, descended from Modified Wisconsin Line 3, were obtained from Dr W. In addition to daily health monitoring, fresh food and water were provided ad libitum. Experimental animals were euthanized by insufflation of isoflurane gas (Butler, Dublin, OH)
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