A temporal shift in regulatory networks and pathways in the bovine small intestine during Cooperia oncophora infection
dataset
posted on 2024-11-23, 21:28authored byBovine Functional Genomics Laboratory, Animal & Natural Resources Institute, USDA
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. Overall design: A total of 20 arrays were used in a time series experiment. Four biological replicates (animals) were used for each time point including naive control (unfected)
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