Disease tolerance and immune response in bovine trypanosomiasis is mediated by CD14 promoter gene

Abstract

Abstract Bovine trypanosomiasis is a major drawback for cattle production in sub-Saharan Africa. Immune response to infection is thought to be mediated by genetic diversity in pattern recognition receptors, leading to disease tolerance or susceptibility. We elucidated naturally occurring variations within the bovine CD14 gene promoter in trypanotolerant (N’dama) and trypanosusceptible (White Fulani) cattle, using genomic and transcriptomic methods. We compared our gene sequences with reference bovine genome UMD 3.1 assembly from the Ensembl database. In all, we identified a total of 54 and 41 SNPs at the CD14 promoter for Ndama and White Fulani respectively, including 10 (rs210109064, rs473185091, rs521360374, rs454858160, rs432371570, rs446947915, rs442402639 and rs456854916) common to both. Interestingly, we found 36 SNP’s in 9 SNP regions that were unique to Ndama that were either functional or transcript overlap variants. The significantly higher SNP variation and density at the CD14 promoter region in Ndama could be responsible for its trypanotolerance, potentially an evolutionary adaptation to disease. To further validate this, we examined the expression of CD14 in tissue samples, with our results showing a significant upregulation and higher expression in Ndama compared to White Fulani (p<0.05). These results confirm that trypanotolerant Ndama significantly expressed CD14 and the presence of a higher SNP variation at the CD14 gene promoter plays an important role in pathogen recognition and initiation of immune response, which is absent in White Fulani (trypanosusceptible). This is a major player in host defense mechanism against trypanosomiasis that could be harnessed for breeding and selection purposes.