A temporal shift in regulatory networks and pathways in the bovine small intestine during Cooperia oncophora infection

Authors: Li, Robert; Gasbarre, Louis

Submitted to: International Journal for Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/21/2008
Publication Date: 6/1/2009
Citation: Li, R.W., Gasbarre, L.C. 2009. A temporal shift in regulatory networks and pathways in the bovine small intestine during Cooperia oncophora infection. International Journal for Parasitology. 39:813-824.

Interpretive Summary: Internal parasites, especially gastrointestinal nematodes, have been ranked among the top three diseases or conditions that may have a significant economic impact on the American cattle industry with the estimated annual cost in excess of $2 billion per year in lost productivity and increased operating expenses. Cooperia oncophora is an important parasitic nematode of ruminants with a worldwide distribution. Limited knowledge in our understanding of host-parasite relationship and host immune response has hindered the development of novel nematode control strategies such as vaccines or immunomodulators. In this study, we conducted a holistic analysis of the transcriptome of the bovine small intestine during parasite infection. We identified a total of 310 genes, 22 canonical pathways, and 9 regulatory networks significantly affected by the infection. Our results provide insight into protective immunity against gastrointestinal nematodes and a molecular roadmap for the future study in defining host immune responses.

Technical Abstract: Cooperia oncophora is an important parasitic nematode of ruminants with a worldwide distribution. Twenty Holstein nematode-naïve 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. The pathways and regulatory networks significantly impacted by the infection were analyzed. A total of 22 canonical pathways and 9 regulatory networks 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 TGFß 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.