Bovine Functional Genomics Laboratory, U.S. Department of Agriculture-Agricultural Research Service, BARC East, Beltsville, MD 20705, USA.
Int J Parasitol. 2009 Jun;39(7):813-24. doi: 10.1016/j.ijpara.2008.11.007. Epub 2008 Dec 11.
Cooperia oncophora is an important parasitic nematode of cattle with a wide distribution in temperate areas. Twenty Holstein nematode-naïve bull calves were experimentally infected with approximately 100,000 infective L3s and infection was allowed to progress for 7, 14, 28, 42 days, respectively. This experiment was conducted to identify putative recognition and inflammatory pathways in the host-parasite relationship. Gene expression profiles of the small intestine were compared using a high-density bovine 60 mer oligo microarray. A total of 310 genes were differentially expressed during the course of infection. The pathways and regulatory networks significantly impacted by the infection were analysed. A total of 22 canonical pathways and nine regulatory networks were significantly affected during infection. During the early phase of the infection (7 days p.i.), parasites suppressed the acute phase response and the complement system of the host. At 14 days p.i., three out of the six pathways impacted were related with retinoid X receptor (RXR) functions. At 28 days p.i., the effects on RXR were less evident. The host response shifted to lipid metabolism and signalling, especially eicosanoid production and signalling, suggesting that eicosanoid-mediated inflammation might be a major host defence mechanism. By 42 days p.i., the pathways impacted involved glycosphingolipid biosynthesis and transforming growth factor beta (TGFbeta signalling. The expression of cadherin-like 26 (CDH26) was strongly up-regulated starting at 14 days p.i. and peaked at 28 days p.i. The extent of its expression is positively correlated with the infiltration of eosinophils (R=0.82) and coincides with the number 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 that it may serve as a pattern recognition molecule for C. oncophora. These results provide a potential molecular roadmap for future studies aimed at defining host immune responses and understanding protective immunity against gastrointestinal nematodes.
细颈囊尾蚴是一种分布广泛的重要寄生性牛线虫，感染后可引起牛的慢性腹泻。本研究用大约 10 万条感染性第 3 期幼虫（L3）对 20 头未曾感染过囊尾蚴的荷斯坦公牛犊进行了人工感染，分别于感染后第 7、14、28、42 天采集小肠组织，以研究宿主 - 寄生虫相互关系中的识别和炎症相关途径。利用牛 60mer 寡核苷酸微阵列比较了小肠的基因表达谱。在感染过程中，共发现 310 个基因发生差异表达。分析了感染显著影响的途径和调控网络。感染过程中共有 22 条经典途径和 9 个调控网络受到显著影响。在感染的早期阶段（感染后第 7 天），寄生虫抑制了宿主的急性期反应和补体系统。在感染后第 14 天，受影响的 6 条途径中有 3 条与视黄醇 X 受体（RXR）功能有关。在感染后第 28 天，RXR 的影响不明显。宿主的反应转向脂质代谢和信号转导，特别是类二十烷酸的产生和信号转导，表明类二十烷酸介导的炎症可能是主要的宿主防御机制。在感染后第 42 天，受影响的途径涉及糖脂生物合成和转化生长因子β（TGFβ）信号转导。从感染后第 14 天开始，钙粘蛋白样 26（CDH26）的表达强烈上调，并在感染后第 28 天达到高峰。其表达水平与嗜酸性粒细胞的浸润程度呈正相关（R=0.82），与组织中的成虫数量一致。CDH26 的表达谱与另外两种参与识别外来生物体碳水化合物的细胞粘附分子（即凝集素和半乳糖凝集素）相似，表明它可能作为细颈囊尾蚴的模式识别分子。这些结果为未来研究宿主免疫反应和理解抗胃肠道线虫保护性免疫提供了潜在的分子途径。
