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3 results on '"Atsuhi, Kobayashi"'

1. Upregulation of PD-L1 Expression by Prostaglandin E2 and the Enhancement of IFN-γ by Anti-PD-L1 Antibody Combined With a COX-2 Inhibitor in Mycoplasma bovis Infection

Author

Shinya Goto, Satoru Konnai, Yuki Hirano, Junko Kohara, Tomohiro Okagawa, Naoya Maekawa, Yamato Sajiki, Kei Watari, Erina Minato, Atsuhi Kobayashi, Satoshi Gondaira, Hidetoshi Higuchi, Masateru Koiwa, Motoshi Tajima, Eiji Taguchi, Ryoko Uemura, Shinji Yamada, Mika K. Kaneko, Yukinari Kato, Keiichi Yamamoto, Mikihiro Toda, Yasuhiko Suzuki, Shiro Murata, and Kazuhiko Ohashi

Subjects
immunoinhibitory molecules, PD-1, PD-L1, T-cell exhaustion, prostaglandin E2, immune dysfunction, Veterinary medicine, SF600-1100
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 E2 (PGE2) 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 PGE2 in immune dysfunction and the relationship between PGE2 and the PD-1/PD-L1 pathway in M. bovis infection. In vitro stimulation with M. bovis upregulated the expressions of PGE2 and PD-L1 presumably via Toll-like receptor 2 in bovine peripheral blood mononuclear cells (PBMCs). PGE2 levels of peripheral blood in infected cattle were significantly increased compared with those in uninfected cattle. Remarkably, plasma PGE2 levels were positively correlated with the proportions of PD-L1+ monocytes in M. bovis-infected cattle. Additionally, plasma PGE2 production in infected cattle was negatively correlated with M. bovis-specific interferon (IFN)-γ production from PBMCs. These results suggest that PGE2 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-γ response. Our study findings might contribute to the development of novel therapeutic strategies for bovine mycoplasmosis that target PGE2 and the PD-1/PD-L1 pathway.

Published
2020
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2. Clinical efficacy of the combined treatment of anti-PD-L1 rat-bovine chimeric antibody with a COX-2 inhibitor in calves infected with Mycoplasma bovis

Author

Shinya, Goto, Satoru, Konnai, Yuki, Hirano, Junko, Kohara, Tomohiro, Okagawa, Naoya, Maekawa, Yamato, Sajiki, Kei, Watari, Erina, Minato, Atsuhi, Kobayashi, Satoshi, Gondaira, Hidetoshi, Higuchi, Masateru, Koiwa, Motoshi, Tajima, Eiji, Taguchi, Masaru, Ishida, Ryoko, Uemura, Shinji, Yamada, Mika, K. Kaneko, Yukinari, Kato, Keiichi, Yamamoto, Mikihiro, Toda, Yasuhiko, Suzuki, Shiro, Murata, and Kazuhiko, Ohashi

Subjects
Mycoplasma bovis, PD-L1, Immunotherapy, PGE2, COX-2 inhibitor
Published
2020

3. Direct evidence of preventive effect of severe diarrhea in calf by milk replacer-based probiotic feeding

Author

Mitsuru Honma, Tomohiro Okagawa, Haruka Noda, Satoru Konnai, Ganbaatar Otgontuya, Akira Takeda, Manabu Kubota, Junko Kohara, Naoya Maekawa, Hayato Nakamura, Yamato Sajiki, Fumi Kayasaki, Erina Minato, Honami Shimakura, Shiro Murata, Shinya Goto, Nobuhiro Terasaki, Kazuhiko Ohashi, Kei Watari, and Atsuhi Kobayashi

Subjects
medicine.medical_specialty, Probiotic, business.industry, law, Internal medicine, Medicine, Severe diarrhea, business, Gastroenterology, law.invention
Abstract

Background Diarrhea is one of the major causes of death in calves directly linked to economic loss in cattle industry. Fermented milk has been widely used for calf feeding to reduce the diarrhea in clinical settings. However, the fermentation of raw milk has many difficulties, such as unstable fermentation due to large variances of nutrient composition in raw milk and contamination with coliform. Practical use of fermented milk replacer (FMR) has a strong potential to overcome these difficulties. However, the clinical efficacy of FMR on calf diarrhea is still unclear. Result In this study, we developed a stable condition of fermentation for FMR and verified the preventive effects of FMR feeding on calf diarrhea by an experimental infection model of bovine rotavirus (BRV) in newborn calf and a field study in dairy farms with calf diarrhea. Additionally, the clinical efficacy of lactic acid bacteria (LAB)-supplemented milk replacer (LAB-MR) was also evaluated in the experimental infection model. In the experimental infection model, control calves fed a milk replacer showed severe watery diarrhea after BRV challenge. Two out of three control calves were died after rapid decline of milk intake. In contrast, calves fed FMR or high-concentrated LAB-MR showed diarrhea, but the water content of feces was low and stable. In addition, the amount of milk intake decreased temporarily, but recovered immediately in the FMR- or LAB-MR-fed calves. Histopathological analysis of intestinal tracts revealed mucosal lesions were slighter in the FMR- or LAB-MR-fed calves than in the control calves. In a field study of FMR feeding in dairy farms with mixed infection with BRV and Cryptosporidium parvum, the incidence of enteritis and mortality of calf by enteritis were significantly reduced by the allocation of FMR. Additionally, the FMR-fed calves exhibited shorter duration of treatment, fewer consultations, and lower cost of medical care for enteritis compared with control calves. Conclusion These results suggest that feeding of milk replacer-based probiotics to calves reduces severity of diarrhea and tissue damage to intestinal tracts caused by BRV infection and provides significant clinical benefits for the prevention and treatment of calf diarrhea.

Published
2020
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