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Immun Inflamm Dis. 2017 Sep;5(3):355-363. doi: 10.1002/iid3.173. Epub 2017 May 24.

Increase of cells expressing PD-1 and PD-L1 and enhancement of IFN-γ production via PD-1/PD-L1 blockade in bovine mycoplasmosis.

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Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
Hokkaido Research Organization, Agriculture Research Department, Animal Research Center, Shintoku, Japan.
Department of Regional Innovation, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan.
Division of Bioresources, Research Center for Zoonosis, Hokkaido University, Sapporo, Japan.
Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan.



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.


Bovine mycoplasmosis; IFN-γ; PD-1; PD-L1; immunosuppression

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