| Title: | Upregulation of PD-L1 Expression by Prostaglandin E-2 and the Enhancement of IFN-gamma by Anti-PD-L1 Antibody Combined With a COX-2 Inhibitor in Mycoplasma bovis Infection |
| Authors: | Goto, Shinya Browse this author |
| Konnai, Satoru Browse this author →KAKEN DB |
| Hirano, Yuki Browse this author |
| Kohara, Junko Browse this author |
| Okagawa, Tomohiro Browse this author |
| Maekawa, Naoya Browse this author |
| Sajiki, Yamato Browse this author |
| Watari, Kei Browse this author |
| Minato, Erina Browse this author |
| Kobayashi, Atsuhi Browse this author |
| Gondaira, Satoshi Browse this author |
| Higuchi, Hidetoshi Browse this author |
| Koiwa, Masateru Browse this author |
| Tajima, Motoshi Browse this author |
| Taguchi, Eiji Browse this author |
| Uemura, Ryoko Browse this author |
| Yamada, Shinji Browse this author |
| Kaneko, Mika K. Browse this author |
| Kato, Yukinari Browse this author |
| Yamamoto, Keiichi Browse this author |
| Toda, Mikihiro Browse this author |
| Suzuki, Yasuhiko Browse this author →KAKEN DB |
| Murata, Shiro Browse this author →KAKEN DB |
| Ohashi, Kazuhiko Browse this author →KAKEN DB |
| Keywords: | immunoinhibitory molecules |
| PD-1 |
| PD-L1 |
| T-cell exhaustion |
| prostaglandin E-2 |
| immune dysfunction |
| Mycoplasma bovis |
| cattle |
| Issue Date: | 20-Feb-2020 |
| Publisher: | Frontiers Media |
| Journal Title: | Frontiers in veterinary science |
| Volume: | 7 |
| Start Page: | 12 |
| Publisher DOI: | 10.3389/fvets.2020.00012 |
| Abstract: | 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-L1) pathway is involved in immune dysfunction during M. bovis infection and that prostaglandin E-2 (PGE(2)) suppressed immune responses and upregulated PD-L1 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-L1 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-L1(+) monocytes in M. bovis-infected cattle. Additionally, plasma PGE(2) production in infected cattle was negatively correlated with M. bovis-specific interferon (IFN)-gamma 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-L1 antibody and a cyclooxygenase 2 inhibitor significantly upregulated the M. bovis-specific IFN-gamma 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-L1 pathway. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/78178 |
| Appears in Collections: | 獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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