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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

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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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