Tick saliva-induced programmed death-1 and PD-ligand 1 and its related host immunosuppression

Abstract The tick Rhipicephalus microplus is a harmful parasite of cattle that causes considerable economic losses to the cattle breeding industry. Although R. microplus saliva (Rm-saliva) contains several immunosuppressants, any association between Rm-saliva and the expression of immunoinhibitory m...

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Autores principales: Yamato Sajiki, Satoru Konnai, Yoshinori Ikenaka, Kevin Christian Montecillo Gulay, Atsushi Kobayashi, Luís Fernando Parizi, Benvindo Capela João, Kei Watari, Sotaro Fujisawa, Tomohiro Okagawa, Naoya Maekawa, Carlos Logullo, Itabajara da Silva Vaz, Shiro Murata, Kazuhiko Ohashi
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:638fdda85f414409bc159c27d999af7e2021-12-02T15:23:09ZTick saliva-induced programmed death-1 and PD-ligand 1 and its related host immunosuppression10.1038/s41598-020-80251-y2045-2322https://doaj.org/article/638fdda85f414409bc159c27d999af7e2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80251-yhttps://doaj.org/toc/2045-2322Abstract The tick Rhipicephalus microplus is a harmful parasite of cattle that causes considerable economic losses to the cattle breeding industry. Although R. microplus saliva (Rm-saliva) contains several immunosuppressants, any association between Rm-saliva and the expression of immunoinhibitory molecules, such as programmed death (PD)-1 and PD-ligand 1 (PD-L1), has not been described. In this study, flow cytometric analyses revealed that Rm-saliva upregulated PD-1 expression in T cells and PD-L1 expression in CD14+ and CD11c+ cells in cattle. Additionally, Rm-saliva decreased CD69 expression in T cells and Th1 cytokine production from peripheral blood mononuclear cells. Furthermore, PD-L1 blockade increased IFN-γ production in the presence of Rm-saliva, suggesting that Rm-saliva suppresses Th1 responses via the PD-1/PD-L1 pathway. To reveal the upregulation mechanism of PD-1/PD-L1 by Rm-saliva, we analyzed the function of prostaglandin E2 (PGE2), which is known as an inducer of PD-L1 expression, in Rm-saliva. We found that Rm-saliva contained a high concentration of PGE2, and PGE2 treatment induced PD-L1 expression in CD14+ cells in vitro. Immunohistochemical analyses revealed that PGE2 and PD-L1 expression was upregulated in tick-attached skin in cattle. These data suggest that PGE2 in Rm-saliva has the potential to induce the expression of immunoinhibitory molecules in host immune cells.Yamato SajikiSatoru KonnaiYoshinori IkenakaKevin Christian Montecillo GulayAtsushi KobayashiLuís Fernando PariziBenvindo Capela JoãoKei WatariSotaro FujisawaTomohiro OkagawaNaoya MaekawaCarlos LogulloItabajara da Silva VazShiro MurataKazuhiko OhashiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yamato Sajiki
Satoru Konnai
Yoshinori Ikenaka
Kevin Christian Montecillo Gulay
Atsushi Kobayashi
Luís Fernando Parizi
Benvindo Capela João
Kei Watari
Sotaro Fujisawa
Tomohiro Okagawa
Naoya Maekawa
Carlos Logullo
Itabajara da Silva Vaz
Shiro Murata
Kazuhiko Ohashi
Tick saliva-induced programmed death-1 and PD-ligand 1 and its related host immunosuppression
description Abstract The tick Rhipicephalus microplus is a harmful parasite of cattle that causes considerable economic losses to the cattle breeding industry. Although R. microplus saliva (Rm-saliva) contains several immunosuppressants, any association between Rm-saliva and the expression of immunoinhibitory molecules, such as programmed death (PD)-1 and PD-ligand 1 (PD-L1), has not been described. In this study, flow cytometric analyses revealed that Rm-saliva upregulated PD-1 expression in T cells and PD-L1 expression in CD14+ and CD11c+ cells in cattle. Additionally, Rm-saliva decreased CD69 expression in T cells and Th1 cytokine production from peripheral blood mononuclear cells. Furthermore, PD-L1 blockade increased IFN-γ production in the presence of Rm-saliva, suggesting that Rm-saliva suppresses Th1 responses via the PD-1/PD-L1 pathway. To reveal the upregulation mechanism of PD-1/PD-L1 by Rm-saliva, we analyzed the function of prostaglandin E2 (PGE2), which is known as an inducer of PD-L1 expression, in Rm-saliva. We found that Rm-saliva contained a high concentration of PGE2, and PGE2 treatment induced PD-L1 expression in CD14+ cells in vitro. Immunohistochemical analyses revealed that PGE2 and PD-L1 expression was upregulated in tick-attached skin in cattle. These data suggest that PGE2 in Rm-saliva has the potential to induce the expression of immunoinhibitory molecules in host immune cells.
format article
author Yamato Sajiki
Satoru Konnai
Yoshinori Ikenaka
Kevin Christian Montecillo Gulay
Atsushi Kobayashi
Luís Fernando Parizi
Benvindo Capela João
Kei Watari
Sotaro Fujisawa
Tomohiro Okagawa
Naoya Maekawa
Carlos Logullo
Itabajara da Silva Vaz
Shiro Murata
Kazuhiko Ohashi
author_facet Yamato Sajiki
Satoru Konnai
Yoshinori Ikenaka
Kevin Christian Montecillo Gulay
Atsushi Kobayashi
Luís Fernando Parizi
Benvindo Capela João
Kei Watari
Sotaro Fujisawa
Tomohiro Okagawa
Naoya Maekawa
Carlos Logullo
Itabajara da Silva Vaz
Shiro Murata
Kazuhiko Ohashi
author_sort Yamato Sajiki
title Tick saliva-induced programmed death-1 and PD-ligand 1 and its related host immunosuppression
title_short Tick saliva-induced programmed death-1 and PD-ligand 1 and its related host immunosuppression
title_full Tick saliva-induced programmed death-1 and PD-ligand 1 and its related host immunosuppression
title_fullStr Tick saliva-induced programmed death-1 and PD-ligand 1 and its related host immunosuppression
title_full_unstemmed Tick saliva-induced programmed death-1 and PD-ligand 1 and its related host immunosuppression
title_sort tick saliva-induced programmed death-1 and pd-ligand 1 and its related host immunosuppression
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/638fdda85f414409bc159c27d999af7e
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