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

• Published in: Scientific reports Vol. 11; no. 1; pp. 1063 - 11
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.01.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250; 692/420; Animal husbandry; Apoptosis; Cattle; CD11c antigen; CD14 antigen; CD69 antigen; Cytokines; Ectoparasites; Flow cytometry; Humanities and Social Sciences; Immunosuppression; Immunosuppressive agents; Leukocytes (mononuclear); Ligands; Lymphocytes T; multidisciplinary; Parasites; PD-1 protein; PD-L1 protein; Peripheral blood mononuclear cells; Prostaglandin E2; Saliva; Science; Science (multidisciplinary); γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-80251-y

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.