Submitted to: Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/17/2011
Publication Date: 3/18/2011
Citation: Li, R.W., Li, C., Gasbarre, L.C. 2011. The vitamin D receptor and inducible nitric oxide synthase associated pathways in the development of acquired resistance to Cooperia oncophora infection in cattle. Veterinary Research. 42(1):48. Interpretive Summary: Gastrointestinal parasites have a significant economic impact on the American cattle industry with an estimated annual cost in excess of $2 billion. Limited knowledge in our understanding of host-parasite relationship and acquired resistance has hindered the development of vaccines and immune-modulators. In this study, we conducted a transcriptomic analysis of the bovine small intestine during primary infection and reinfection. We presented evidence that acquired resistance to Cooperia oncophora infection in cattle can be rapidly developed following priming of the immune response. We identified multiple signaling pathways that were significantly impacted during reinfection, which may have contributed significantly to the development of acquired resistance via their potential roles in immune regulation and intestinal mucosal integrity maintenance.
Technical Abstract: Cooperia oncophora is an economically important gastrointestinal nematode in ruminants. Acquired resistance to Cooperia oncophora infection in cattle develops rapidly resulting from prior infections. Naïve cattle, when given a primary infection of high-dose infective L3 larvae, develop a strong immunity to subsequent reinfection. Compared to primary infection, reinfection resulted in a marked reduction in worm establishment. In order to understand molecular mechanisms underlying the development of acquired resistance, we characterized the transcriptomic responses of the bovine small intestine to a primary infection and reinfection. A total of 23 pathways were significantly impacted during infection. The vitamin D receptor activation was strongly induced only during reinfection, suggesting that this pathway may play an important role in the development of acquired resistance via its potential roles in immune regulation and intestinal mucosal integrity maintenance. The expression of inducible nitric oxide synthase (NOS2) was strongly induced during reinfection but now during primary infection. As a result, several canonical pathways associated with NOS2 were impacted. The genes involved in eicosanoid synthesis, including COX2, remained largely unchanged during infection. The rapid development of acquired resistance may help explain the lack of relative pathogenicity by Cooperia oncophora infection in cattle. Our findings will undoubtedly facilitate understanding of molecular mechanisms underlying the development of acquired resistance, which could have an important implication in vaccine design.