Increase of cells expressing PD-1 and PD-L1 and enhancement of IFN-γ production via PD-1/PD-L1 blockade in bovine mycoplasmosis.
Increase of cells expressing PD-1 and PD-L1 and enhancement of IFN-γ production via PD-1/PD-L1 blockade in bovine mycoplasmosis.
复制标题
表达PD-1和PD-L1的细胞增加，以及通过牛支原体中PD-1/PD-L1阻断的IFN-γ产生增强。
DOI：
10.1002/iid3.173
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Ohashi K
中科院分区：
文献类型：
--
作者：
Goto S;Konnai S;Okagawa T;Nishimori A;Maekawa N;Gondaira S;Higuchi H;Koiwa M;Tajima M;Kohara J;Ogasawara S;Kato Y;Suzuki Y;Murata S;Ohashi K
牛支原体（Mycoplasma bovis）是引起牛肺炎、乳腺炎、关节炎和中耳炎的病原体。这种病原体发挥免疫抑制作用，如抑制干扰素的产生。然而，涉及牛支原体病的机制尚未完全阐明。在这项研究中，我们研究了程序性死亡-1（PD-1）/程序性死亡配体1（PD-L1）通路在牛支原体病免疫抑制中的作用。在最初的实验中，我们使用酶联免疫吸附试验测量从支原体病牛中分离的外周血单核细胞（PBMC）中的干扰素-γ（IFN-γ）。与临床健康牛相比，预期支原体病牛的IFN-γ产量显著降低。同时，流式细胞术分析显示，感染牛外周血中PD-1+ CD 4+和PD-L1+ CD 14+细胞的比例显著增加。有趣的是，在牛支原体病中，PD-1+ CD 4+和PD-1+ CD 8 + T细胞的数量与PBMC产生的IFN-γ呈负相关。此外，抗牛PD-1和抗牛PD-L1抗体在体外阻断PD-1/PD-L1通路可显著上调抗支原体特异性细胞的IFN-γ产生。这些结果表明，PD-1/PD-L1通路可能参与牛支原体特异性T细胞的免疫耗竭。总之，我们的研究开辟了一个新的视角，在治疗策略牛支原体病的免疫抑制受体通路为目标。
Bovine mycoplasma, chiefly Mycoplasma bovis, is a pathogen that causes pneumonia, mastitis, arthritis, and otitis media in cattle. This pathogen exerts immunosuppressive effects, such as the inhibition of interferon production. However, the mechanisms involved in bovine mycoplasmosis have not been fully elucidated. In this study, we investigated the role of the programmed death‐1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) pathway in immunosuppression in bovine mycoplasmosis. In the initial experiments, we used enzyme‐linked immunosorbent assay to measure interferon‐γ (IFN‐γ) from peripheral blood mononuclear cells (PBMCs) isolated from cattle with mycoplasmosis. Expectedly, IFN‐γ production significantly decreased in cattle with mycoplasmosis compared with that in clinically healthy cattle. Concomitantly, flow cytometric analysis revealed that the proportions of PD‐1+CD4+ and PD‐L1+CD14+ cells significantly increased in peripheral blood of the infected cattle. Interestingly, the number of PD‐1+CD4+ and PD‐1+CD8+ T cells were negatively correlated with IFN‐γ production from PBMCs in bovine mycoplasmosis. Additionally, blockade of the PD‐1/PD‐L1 pathway in vitro by anti‐bovine PD‐1‐ and anti‐bovine PD‐L1 antibodies significantly upregulated the production of IFN‐γ from anti‐mycoplasma‐specific cells. These results suggest that the PD‐1/PD‐L1 pathway could be involved in immune exhaustion of bovine mycoplasma‐specific T cells. In conclusion, our study opens up a new perspective in the therapeutic strategy for bovine mycoplasmosis by targeting the immunoinhibitory receptor pathways.
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影响因子：
3.7
作者：
Nishimori A;Konnai S;Okagawa T;Maekawa N;Ikebuchi R;Goto S;Sajiki Y;Suzuki Y;Kohara J;Ogasawara S;Kato Y;Murata S;Ohashi K
通讯作者：
Ohashi K
影响因子：
0.8
作者：
Rodriguez, F.;Castro, P.;Fernandez, A.
通讯作者：
Fernandez, A.
DOI：
10.1111/j.1574-695x.2002.tb00540.x
发表时间：
2002-01-14
影响因子：
--
作者：
Vanden Bush, TJ;Rosenbusch, RF
通讯作者：
Rosenbusch, RF
影响因子：
4.4
作者：
Ikebuchi R;Konnai S;Okagawa T;Yokoyama K;Nakajima C;Suzuki Y;Murata S;Ohashi K
通讯作者：
Ohashi K
影响因子：
30.5
作者：
Blackburn, Shawn D.;Shin, Haina;Haining, W. Nicholas;Zou, Tao;Workman, Creg J.;Polley, Antonio;Betts, Michael R.;Freeman, Gordon J.;Vignali, Dario A. A.;Wherry, E. John
通讯作者：
Wherry, E. John