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

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,...

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Detalles Bibliográficos
Autores principales: Sajiki, Yamato, Konnai, Satoru, Ikenaka, Yoshinori, Gulay, Kevin Christian Montecillo, Kobayashi, Atsushi, Parizi, Luís Fernando, João, Benvindo Capela, Watari, Kei, Fujisawa, Sotaro, Okagawa, Tomohiro, Maekawa, Naoya, Logullo, Carlos, da Silva Vaz, Itabajara, Murata, Shiro, Ohashi, Kazuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806669/
https://www.ncbi.nlm.nih.gov/pubmed/33441793
http://dx.doi.org/10.1038/s41598-020-80251-y
Descripción
Sumario: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 E(2) (PGE(2)), which is known as an inducer of PD-L1 expression, in Rm-saliva. We found that Rm-saliva contained a high concentration of PGE(2), and PGE(2) treatment induced PD-L1 expression in CD14(+) cells in vitro. Immunohistochemical analyses revealed that PGE(2) and PD-L1 expression was upregulated in tick-attached skin in cattle. These data suggest that PGE(2) in Rm-saliva has the potential to induce the expression of immunoinhibitory molecules in host immune cells.