Shu Dairu, Subharat Supatsak, Wedlock D Neil, Luo Dongwen, de Lisle Geoffrey W, Buddle Bryce M
AgResearch, Hopkirk Research Institute, Grasslands Research Centre, Private Bag 11008, Palmerston North 4442, New Zealand.
Clin Vaccine Immunol. 2011 Sep;18(9):1467-76. doi: 10.1128/CVI.05201-11. Epub 2011 Jul 27.
Mycobacterium avium subsp. paratuberculosis, the causative agent of Johne's disease, is able to dampen or distort immune responses at the mucosal sites and coexist with a massive infiltration of immune cells in the gastrointestinal tract. Knowledge of the mechanism by which M. avium subsp. paratuberculosis subverts the immune response at the mucosal level in cattle is important for the development of improved disease control strategies, including new vaccines and diagnostic tests. In this study, 38 cull cows from herds infected with M. avium subsp. paratuberculosis were divided into four groups, based on M. avium subsp. paratuberculosis culture from gut tissues and histopathological lesion scores. Cytokine gene expression and secretion from M. avium subsp. paratuberculosis sonicate-stimulated peripheral blood mononuclear cell (PBMC) and mesenteric lymph node (MLN) cultures of the animals were compared. Antigen stimulation of MLN cells from the severely lesioned group resulted in significant upregulation of the mRNA expression of five cytokines, gamma interferon (IFN-γ), interleukin-10 (IL-10), IL-13, IL-17A, and tumor necrosis factor alpha (TNF-α), which have a diverse range of functions, while there was no significant upregulation of these cytokines by the other groups. There were major differences between the responses of the PBMC and MLN cultures, with higher levels of secreted IFN-γ released from the MLN cultures and, conversely, higher levels of IL-10 released from the PBMC cultures. The upregulation of all five cytokines from cells at the site of infection in the severely lesioned animals suggested a dysregulated immune response, contributing to a failure to clear infection in this group of animals.
副结核分枝杆菌是约内氏病的病原体，它能够抑制或扭曲黏膜部位的免疫反应，并与胃肠道中大量免疫细胞浸润共存。了解副结核分枝杆菌在牛的黏膜水平颠覆免疫反应的机制，对于制定改进的疾病控制策略（包括新疫苗和诊断测试）非常重要。在本研究中，从感染副结核分枝杆菌的牛群中选取38头淘汰母牛，根据肠道组织中的副结核分枝杆菌培养物和组织病理学病变评分分为四组。比较了副结核分枝杆菌超声破碎物刺激的动物外周血单核细胞（PBMC）和肠系膜淋巴结（MLN）培养物中细胞因子基因的表达和分泌情况。对严重病变组的MLN细胞进行抗原刺激，导致五种细胞因子（γ干扰素（IFN-γ）、白细胞介素-10（IL-10）、IL-13、IL-17A和肿瘤坏死因子α（TNF-α））的mRNA表达显著上调，这些细胞因子具有多种功能，而其他组这些细胞因子没有显著上调。PBMC和MLN培养物的反应存在主要差异，MLN培养物分泌的IFN-γ水平较高，相反，PBMC培养物释放的IL-10水平较高。严重病变动物感染部位细胞中所有五种细胞因子的上调表明免疫反应失调，导致该组动物无法清除感染。
