Clinical efficacy of the combined treatment of anti-PD-L1 rat-bovine chimeric antibody with a COX-2 inhibitor in calves infected with Mycoplasma bovis
Clinical efficacy of the combined treatment of anti-PD-L1 rat-bovine chimeric antibody with a COX-2 inhibitor in calves infected with Mycoplasma bovis
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DOI：
10.14943/jjvr.68.2.77
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发表时间：
2020-05-01
影响因子：
0.4
通讯作者：
Ohashi, Kazuhiko
中科院分区：
文献类型：
--
作者：
Goto, Shinya;Konnai, Satoru;Ohashi, Kazuhiko
牛支原体（牛支原体）是一种高度传染性病原体，与牛支原体相关的疾病，特别是肺炎，主要以畜群地方性传染病的形式发生，由于小牛死亡率和存活小牛体重下降，造成相当大的经济损失。在我们之前的研究中，我们发现程序性死亡-1 (PD-1)/ pd -配体1 （PD-L1）通路和前列腺素E-2 （PGE(2)）参与了牛慢性传染病免疫抑制。本研究利用抗牛PDLl大鼠-牛嵌合抗体Boch4G12和环氧化酶2 （COX-2）抑制剂美洛昔康，研究了双阻断PD-1/PD-L1途径和PGE(2)在牛支原体感染中的作用。Boch4G12和美洛昔康治疗的小牛在给药后显著增强了牛乳杆菌特异性IFN- γ反应。另一方面，在整个实验期间，对照组和单独使用美洛昔康的牛的ifn - γ反应没有被激活。有趣的是，用Boch4G12加或不加美洛昔康治疗的小牛鼻分泌物和支气管肺泡灌洗液中的细菌负荷显著降低。这些结果表明，抗pd - l1抗体与COX-2抑制剂的组合是治疗牛支原体感染小牛的候选药物。
Mycoplasma bovis (M. bovis) is a highly contagious pathogen and M. bovis-associated diseases, particularly pneumonia, occur predominantly as herd enzootics, causing considerable economic losses because of calf mortality, weight loss in surviving calves. In our previous studies, the programmed death-1 (PD-1)/ PD-ligand 1 (PD-L1) pathway and prostaglandin E-2 (PGE(2)) were shown to be involved in the immunosuppression during chronic infectious diseases in cattle. In this study, the efficacy of dual blockade of the PD-1/PD-L1 pathway and PGE(2) in M. bovis infection in vivo was investigated using anti-bovine PDLl rat-bovine chimeric antibody, Boch4G12, and cyclooxygenase 2 (COX-2) inhibitor, meloxicam. The calves treated with Boch4G12 and meloxicam significantly enhanced M. bovis-specific IFN--gamma response after the administration. On the other hand, IFN-gamma response was not activated in the controls and cattle treated with meloxicam alone throughout the experimental period. Interestingly, bacterial loads in nasal discharge and bronchoalveolar lavage fluid among calves treated with Boch4G12 with or without meloxicam were significantly decreased. These results suggest that the combination of anti-PD-L1 antibody with a COX-2 inhibitor is a candidate for therapeutic applications in calves infected with M. bovis.