The immune system is a complex network of cells and molecules protecting the host against pathogens in a delicately coordinated process. Diversity in response and different layers of defence mechanisms ensure survival of the host in the face of diverse pathogen challenge. This system is controlled by more than 6000 genes, making the immune system complex in terms of understanding the nuances of its genetic regulation. Resistance to disease is even more complicated as pathogens have their own set of genes that interact with the immune system in any given environment. Advances in genomic methods have opened a new opportunity to study genetic regulation at the cellular level. Utilizing this concept to study the cells of the immune system in the face of pathogenic challenge is a useful approach to examine the genetics of disease resistance. In the current study, two bactericidal responses of bovine monocyte-derived macrophages (MDMs), nitric oxide production (NO-) and phagocytosis, against Escherichia coli, were investigated. The results demonstrated notable individual variation for both responses (coefficient of variation 35% in phagocytosis ability and 65% in production of NO-); as well as a strong, significant, and positive correlation between NO- production and phagocytosis (Spearsman’s rank correlation: p value = 0.01, ρ = 0.62). At the next step, MDMs derived from 8 Holstein cows were divided into high, average, and low responder phenotypes, based on their production of NO-. The MDM transcriptome of these three phenotypes were compared to the untreated controls at 3 hours after E. coli challenge. More than 1300 genes were identified to be differentially expressed after the challenge (FDR p-value ≤ 0.05). The gene ontology analysis revealed different underlying molecular mechanism that are associated with impaired or enhanced ability to elicit bactericidal response. Of particular interest was the anti-inflammatory pathway which includes the production of IL10 that was enriched in the low and average responder phenotypes, while genes in the Tumour Necrosis Factor - α pathway, a master regulator of pro-inflammatory cytokine production, were enriched in MDMs of the high responder phenotype. The findings from this study showed the possibility of using a cellular immuno-genomic approach to examine immune functions in cattle. The next step of this study will be investigating the genetic polymorphisms within bovine MDMs that are causing or associated with the gene expressions and pathways that were found to be associated with the high, average or low phenotypes based on NO- production. Keywords: Macrophage, Disease Resistance, RNA-Seq, Cattle, Nitric oxide production, phagocytosis
Proceedings of the World Congress on Genetics Applied to Livestock Production, Volume Electronic Poster Session - Biology - Disease Resistance 1, , 738, 2018
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