The Roslin Institute and R(D)SVS, University of Edinburgh, Roslin, Midlothian, EH25 9RG, Scotland, UK.
Vet Res. 2011 Jun 17;42(1):78. doi: 10.1186/1297-9716-42-78.
Infection of sheep with the gastric nematode Teladorsagia circumcincta results in distinct Th2-type changes in the mucosa, including mucous neck cell and mast cell hyperplasia, eosinophilia, recruitment of IgA/IgE producing cells and neutrophils, altered T-cell subsets and mucosal hypertrophy. To address the protective mechanisms generated in animals on previous exposure to this parasite, gene expression profiling was carried out using samples of abomasal mucosa collected pre- and post- challenge from animals of differing immune status, using an experimental model of T. circumcincta infection. Recently developed ovine cDNA arrays were used to compare the abomasal responses of sheep immunised by trickle infection with worm-naïve sheep, following a single oral challenge of 50 000 T. circumcincta L3. Key changes were validated using qRT-PCR techniques. Immune animals demonstrated highly significant increases in levels of transcripts normally associated with cytotoxicity such as granulysin and granzymes A, B and H, as well as mucous-cell derived transcripts, predominantly calcium-activated chloride channel 1 (CLCA1). Challenge infection also induced up-regulation of transcripts potentially involved in initiating or modulating the immune response, such as heat shock proteins, complement factors and the chemokine CCL2. In contrast, there was marked infection-associated down-regulation of gene expression of members of the gastric lysozyme family. The changes in gene expression levels described here may reflect roles in direct anti-parasitic effects, immuno-modulation or tissue repair.
绵羊感染胃线虫后，黏膜会发生明显的 Th2 型变化，包括黏液颈细胞和肥大细胞增生、嗜酸性粒细胞增多、IgA/IgE 产生细胞和中性粒细胞募集、T 细胞亚群改变和黏膜肥大。为了研究先前暴露于这种寄生虫的动物产生的保护机制，我们使用来自具有不同免疫状态的动物的胃黏膜样本，使用一种胃线虫感染的实验模型，进行了基于基因表达谱的研究。我们使用最近开发的绵羊 cDNA 芯片，比较了经滴注感染免疫的绵羊与未感染绵羊在单次口服 50,000 条 T. circumcincta L3 后的胃黏膜反应。使用 qRT-PCR 技术验证了关键变化。免疫动物表现出与细胞毒性相关的转录物水平的显著增加，例如颗粒溶素和颗粒酶 A、B 和 H，以及黏液细胞衍生的转录物，主要是钙激活氯离子通道 1 (CLCA1)。挑战感染还诱导了潜在参与启动或调节免疫反应的转录物的上调，例如热休克蛋白、补体因子和趋化因子 CCL2。相比之下，胃溶菌酶家族成员的基因表达在感染相关下调中显著下调。这里描述的基因表达水平变化可能反映了直接抗寄生虫作用、免疫调节或组织修复的作用。
