@article{oai:rakuno.repo.nii.ac.jp:00006812,
 author = {Goto, Shinya and Konnai, Satoru and Hirano, Yuki and Kohara, Junko and Okagawa, Tomohiro and Maekawa, Naoya and Sajiki, Yamato and Watari, Kei and Minato, Erina and Kobayashi, Atsuhi and Gondaira, Satoshi and 権平, 智 and 樋口, 豪紀 and Koiwa, Masateru and 田島, 誉士 and Taguchi, Eiji and Uemura, Ryoko and Yamada, Shinji and Kaneko, Mika K. and Kato, Yukinari and Yamamoto, Keiichi and Toda, Mikihiro and Suzuki, Yasuhiko and Murata, Shiro and Ohashi, Kazuhiko},
 journal = {Frontiers in Veterinary Science},
 month = {Feb},
 note = {Article, Bovine mycoplasmosis caused by Mycoplasma bovis results in pneumonia and mastitis in cattle. We previously demonstrated that the programmed death_1 (PD_<-1>)/PD-ligand _1 (PD-L_1) pathway is involved in immune dysfunction during M. bovis infection and that prostaglandin E_2 (PGE_2) suppressed immune responses and upregulated PD-L_1 expression in Johne's disease, a bacterial infection in cattle. In this study, we investigated the role of PGE_2 in immune dysfunction and the relationship between PGE_2 and the PD-1/PD-L1 pathway in M. bovis infection. In vitro stimulation with M. bovis upregulated the expressions of PGE_2 and PD-L_1 presumably via Toll-like receptor 2 in bovine peripheral blood mononuclear cells (PBMCs). PGE_2 levels of peripheral blood in infected cattle were significantly increased compared with those in uninfected cattle. Remarkably, plasma PGE_2 levels were positively correlated with the proportions of PD-L_1^+ monocytes in M. bovis-infected cattle. Additionally, plasma PGE_2 production in infected cattle was negatively correlated with M. bovis-specific interferon (IFN)-γ production from PBMCs. These results suggest that PGE_2 could be one of the inducers of PD-L1 expression and could be involved in immunosuppression during M. bovis infection. In vitro blockade assays using anti-bovine PD-L_1 antibody and a cyclooxygenase 2 inhibitor significantly upregulated the M. bovis-specific IFN-γ response. Our study findings might contribute to the development of novel therapeutic strategies for bovine mycoplasmosis that target PGE_2 and the PD_<-1>/PD-L_1 pathway.},
 pages = {12-1--12-14},
 title = {Upregulation of PD-L1 Expression by Prostaglandin E_2 and the Enhancement of IFN-γ by Anti-PD-L1 Antibody Combined With a COX-2 Inhibitor in Mycoplasma bovis Infection},
 volume = {7},
 year = {2020}
}