Abstract
IntroductionBovine 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.MethodsIn 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.ResultsExpectedly, 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.ConclusionsThese 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.
Highlights
Bovine mycoplasma, Mycoplasma bovis, is a pathogen that causes pneumonia, mastitis, arthritis, and otitis media in cattle
No significant differences were observed in IFN-g production among the different clinical symptoms in the M. bovis-infected cattle
To investigate PD-1 expression in bovine mycoplasmosis, we examined the proportions of PD-1þ cells among peripheral blood mononuclear cell (PBMC)
Summary
Research Promotion Program for Agriculture, Forestry, Fisheries, and Food Industry, Japan (grant 26058B to S.K.) and the NARO, Biooriented Technology Research Advancement. Institution (the special scheme project on regional developing strategy: grant 16817557 to S.K.). Final version published online 24 May 2017. Ethical approval: The authors of this study did not perform experiments with human participants or animals
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