Project description:Cooperia oncophora is an economically important gastrointestinal nematode in ruminants. Acquired resistance to Cooperia oncophora infection in cattle develops rapidly as a result of 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 prostaglandin synthase 2 (PTGS2 or 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. The transcriptomic profiles of the bovine small intestine in response to both a primary infection and a drug-attenuated reinfection were compared. The data were analyzed using the same condition and procedure. The gene expression profiles of calves 14 days after a primary Cooperia oncophora infection and a drug-attenuated reinfection were compared to their respective age-matched controls (naive controls and drug-drenched worm-free controls)

Project description:Cooperia oncophora is an important parasitic nematode of ruminants with a worldwide distribution. Twenty Holstein nematode-naive bull calves were experimentally infected with approximately 100,000 L3 stage infective larvae for 7, 14, 28, 42 days, respectively. The experiment was conducted in order to identify putative recognition and inflammatory pathways in the host-parasite relationship. Gene expression profiles in the small intestine were compared using a high-density bovine 60mer oligo microarray. A total of 310 sequences were differentially expressed during the course of infection (P<0.05). The pathways and regulatory networks significantly impacted by the infection were analyzed. A total of 22 canonical pathways (P<0.05) and 9 regulatory networks (P<10-10) were significantly affected by the infection. At the early phase of the infection (7 days post infection, 7dpi), the parasites suppressed acute phase response and complement system in the host. At 14dpi, three out of the six pathways impacted were related with RXR functions. When the infection progressed to 28dpi, the RXR functions started to fade away. The host response was shifted to lipid metabolism and signaling, especially eicosanoid production and signaling, suggesting eicosanoid-mediated inflammation possibly emerging as a major host defense mechanism. By 42dpi, the pathways impacted involved glycosphingolipid biosynthesis and TGFbeta signaling. The expression of cadherin-like 26 (CDH26) was strongly up-regulated starting at 14dpi and peaked at 28dpi with a ~150-fold increase. The extent of its expression is positively correlated with the infiltration of eosinophils (R =0.82), and in addition, coincides with the numbers of adult parasites in the tissue. CDH26 demonstrated an expression profile similar to two other cell adhesion molecules involved in recognition of carbohydrates on foreign organisms, collectin and galectin, suggesting it may serve as a pattern recognition molecule for Cooperia oncophora. Our results will undoubtedly provide a molecular roadmap for the future study in defining host immune responses and understanding protective immunity against gastrointestinal nematodes.

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Cooperia oncophora

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