Differential cytokine gene expression profiles in the three pathological forms of sheep paratuberculosis.
Differential cytokine gene expression profiles in the three pathological forms of sheep paratuberculosis.
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DOI：
10.1186/1746-6148-3-18
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发表时间：
2007-08-14
影响因子：
2.6
通讯作者：
Hopkins, John
中科院分区：
文献类型：
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作者：
Smeed, Jennifer A;Watkins, Craig A;Hopkins, John
背景技术背景：约内氏病是由鸟分枝杆菌副结核亚种（MAP）感染引起的肠道慢性炎症性疾病。症状包括消瘦、腹泻、身体状况恶化和最终死亡。在绵羊中描述了三种形式的约翰氏病-少杆菌型、多杆菌型和无症状型。少杆菌型的特征在于炎症性Th 1型免疫应答。该疾病的多杆菌形式传播感染，其特征在于由Th 2型免疫应答介导的巨噬细胞浸润，并且无症状的动物没有临床症状或病理学，但感染了MAP。是什么决定了这三种形式的疾病是未知的。为了进一步了解这些差异，我们使用实时RT-PCR比较了13种细胞因子和精氨酸相关基因在回肠组织中的表达，从绵羊与三种形式的diseases.Results：三种病理形式的羊副结核病的定义的基础上，组织病理学，细胞化学（Zeihl-Neelsen）和IS 900 PCR。少杆菌性病变有大量T细胞和嗜酸性粒细胞浸润，ZN阴性;多杆菌性病变有巨噬细胞浸润和大量抗酸菌。少菌型和多菌型分别与IFN γ和IL-10的差异表达有关。此外，两种疾病形式中促炎细胞因子（IL-1 β和TNF α）、IL-8、IL-18和TRAF-1水平的增加指示持续性炎性病变。在任何绵羊回肠组织中均未观察到IL-1 α的变化。无症状的动物是IS 900+与正常的组织学，但有显着降低的IL-18水平和增加的水平TNFalpha.CONCLUSION：我们已经量化了13种细胞因子和细胞因子相关基因的表达水平在三种形式的绵羊副结核病使用实时PCR分析，并确认绵羊少菌性和多菌性疾病分别与1型和2型T细胞反应。其他细胞因子的表达模式表明，这两种疾病的形式有一个炎性病因，但在牛副结核病的IL-1 α的核心作用是没有看到在绵羊感染。无症状的动物被感染，并且没有显示出病理学，但是可以在细胞因子表达模式方面与未感染的对照区分开。
BACKGROUND: Johne's disease is a chronic inflammatory disease of the gut caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP). Symptoms include wasting, diarrhoea, loss of condition and eventual death. Three forms of Johne's disease have been described in sheep - paucibacillary, multibacillary and asymptomatic. The paucibacillary form is characterized by an inflammatory, Th1-type immune response. The multibacillary form of the disease, which disseminates the infection, is characterized by macrophage infiltration mediated by a Th2-type immune response, and asymptomatic animals have no clinical symptoms or pathology but are infected with MAP. What determines these three forms of the disease is unknown. To further understand these differences, we used real-time RT-PCR to compare the expression of thirteen cytokine and cytokine-related genes in ileal tissue from sheep with the three forms of the disease.RESULTS: Three pathological forms of sheep paratuberculosis were defined on the basis of histopathology, cytochemistry (Zeihl-Neelsen) and IS900 PCR. Paucibacillary lesions have largely T cell and eosinophil infiltration and are ZN negative; multibacillary lesions have macrophage infiltration and large numbers of acid-fast bacteria. The pauci- and multibacillary forms are linked to the differential expression of IFN gamma and IL-10 respectively. In addition the increased levels of the proinflammatory cytokines (IL-1 beta and TNFalpha), IL-8, IL-18 and TRAF-1 in both diseased forms is indicative of persistent inflammatory lesions. No changes were seen in IL-1 alpha in any sheep ileum tissues. Asymptomatic animals are IS900+ with normal histology but have significantly decreased levels of IL-18 and increased levels TNFalpha.CONCLUSION: We have quantified the expression levels of thirteen cytokine and cytokine related genes in three forms of ovine paratuberculosis using real-time PCR analyses and confirm that sheep pauci- and multibacillary disease are linked to type 1 and type 2 T cell responses respectively. The expression patterns of other cytokines shows that both disease forms have an inflammatory aetiology but that the central role for IL-1 alpha in bovine paratuberculosis is not seen in the sheep infection. Asymptomatic animals are infected and show no pathology but can be distinguished, in terms of cytokine expression pattern, from uninfected controls.