Sharma Shalini, Sharma Khushbu, Kumar Ram, Dayal Deen, Dhanda Shweta, Kumar Naveen, Chaubey Kundan Kumar, Singh Shoor Vir, Banger Sikander, Sharma Vishal
Department of Veterinary Physiology and Biochemistry, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar 125004, India.
National Centre for Veterinary Type Cultures, ICAR-NRC on Equines Sirsa Road, Hisar 125001, India.
Pathogens. 2024 Jun 4;13(6):473. doi: 10.3390/pathogens13060473.
subspecies (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 IS 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
亚种（MAP）感染会导致慢性、持续性肉芽肿性肠炎，引起长期腹泻和消瘦。该疾病通过使用抗生素、活疫苗、分枝杆菌噬菌体疗法等药物及其他治疗方法进行管理；然而，相当一部分受影响的动物采用这种方法并无改善。我们推测免疫抑制受体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个核细胞（PBMCs）上上调，这可能导致免疫耗竭。从32头疑似MAP感染的腹泻牛中采集样本（血液和粪便）；从哈里亚纳邦希萨尔的奶牛场选取8头明显健康的水牛，以及从流浪牛棚中饲养的14头奶牛（患有慢性腹泻、虚弱和消瘦）。使用本土酶联免疫吸附测定法（i-ELISA）、粪便IS聚合酶链反应、培养和抗酸染色来评估MAP感染。使用定量逆转录聚合酶链反应（qRT-PCR）测定PBMCs上TIM-3和PD-1基因的表达。与明显健康的动物和其他MAP血清阴性腹泻动物相比，5个慢性腹泻PBMCs样本（MAP血清阳性）中TIM3表达相对较高（约400倍、330倍、112倍、65倍和16倍），4个腹泻MAP血清阳性动物中PD-1表达较高（约7倍、1.75倍、2.5倍、7.6倍）。在慢性腹泻、消瘦的流浪牛中也记录到TIM-3和PD-1水平的高共表达。了解现场条件下的免疫反应可能有助于对……进行治疗管理
