PDF(Pubmed)
Abstract：
Mycobacterium avium subspecies paratuberculosis (MAP) infection leads to chronic, persistent granulomatous enteritis, causing prolonged diarrhoea and emaciation. The disease is managed using medications such as antibiotics, live vaccines, mycobacteriophage therapies and other treatments; however, a notable proportion of affected animals do not show improvement with this approach. We hypothesise that immunoinhibitory receptors TIM-3 (T cell immunoglobulin mucin protein-3) and PD-1 (Programmed death receptor 1) may be upregulated on Peripheral blood mononuclear cells (PBMCs) of MAP-seropositive bovines, potentially contributing to immune exhaustion. Samples (blood and faeces) were collected from 32 diarrhoeic bovines suspected of MAP infection; eight apparently healthy buffaloes from the dairy farm at Hisar, Haryana and from 14 cows (suffering from chronic diarrhoea, weakness and emaciation) housed in stray cattle shed. MAP infection was estimated using indigenous ELISA (i-ELISA), faecal IS900 PCR, culture and acid-fast staining. TIM-3 and PD-1 gene expression on PBMCs were determined using qRT-PCR. TIM3 expression was relatively higher (~400-fold, 330-fold, 112-fold, 65-fold and 16-fold) in 5 chronically diarrhoeic PBMCs samples (MAP-seropositive), and higher PD-1 expression (around ~7-fold, 1.75-fold, 2.5-fold, 7.6-fold) was recorded in 4 diarrhoeic MAP-seropositive animals, compared to apparently healthy and other MAP-seronegative diarrhoeic animals. High co-expression of TIM-3 and PD-1 levels was also recorded in chronically diarrhoeic, emaciated stray cattle. Understanding immune responses in field conditions might aid in the therapeutic management of paratuberculosis.
摘要：
鸟分枝杆菌亚种副结核（MAP）感染导致慢性，持续性肉芽肿性肠炎,导致长期腹泻和消瘦。这种疾病是用抗生素等药物治疗的，活疫苗,分枝杆菌噬菌体疗法和其他疗法;然而，相当比例的受影响动物用这种方法没有表现出改善。我们假设免疫抑制受体TIM-3（T细胞免疫球蛋白粘蛋白-3）和PD-1（程序性死亡受体1）可能在MAP血清阳性牛的外周血单核细胞（PBMC）上上调，可能导致免疫衰竭。从32只疑似MAP感染的腹泻牛中收集样本（血液和粪便）；来自Hisar奶牛场的八只明显健康的水牛，哈里亚纳邦和14头奶牛(患有慢性腹泻，虚弱和消瘦)住在流浪牛棚里。使用土著ELISA（i-ELISA）估计MAP感染，粪便IS900PCR，培养和抗酸染色。使用qRT-PCR测定PBMC上的TIM-3和PD-1基因表达。TIM3表达相对较高(~400倍，330折，112倍，65倍和16倍）在5个慢性腹泻PBMC样品（MAP血清阳性）中，和更高的PD-1表达(约7倍，1.75倍，2.5倍，7.6倍）在4只腹泻MAP血清阳性动物中记录，与明显健康和其他MAP血清阴性腹泻动物相比。在慢性腹泻中也记录了TIM-3和PD-1水平的高共表达，瘦弱的流浪牛。了解野外条件下的免疫反应可能有助于副结核病的治疗管理。
