Immunomodulatory effects of Rhipicephalus haemaphysaloides serpin RHS2 on host immune responses

Immunomodulatory effects of Rhipicephalus haemaphysaloides serpin RHS2 on host immune responses
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扇头扇贝丝氨酸蛋白酶抑制剂 RHS2 对宿主免疫反应的免疫调节作用

DOI:
10.1186/s13071-019-3607-4
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发表时间:
2019-07
影响因子:
3.2
通讯作者:
Zhou Jinlin
Zhou Jinlin
中科院分区:
医学2区
文献类型:
--
作者:
Xu Zhengmao;Lin Zhibing;Wei Nana;Di Qing;Cao Jie;Zhou Yongzhi;Gong Haiyan;Zhang Houshuang;Zhou Jinlin

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血蜱扇头蜱是中国和其他东南亚国家广泛分布的蜱种,是许多病原体的媒介。本研究的目的是研究丝氨酸蛋白酶抑制剂(丝氨酸蛋白酶抑制剂)在蜱与宿主相互作用中的作用。体外诱导骨髓源性树突状细胞(BMDC)分化,并评估RHS2对DC成熟的影响。通过流式细胞术分析 RHS2 对 T 细胞活化和细胞毒性 T 淋巴细胞 (CTL) 活性的影响。测定用RHS2和OVA免疫小鼠后的抗体亚型。 RHS2可以抑制骨髓源性细胞向DC的分化,并促进其向巨噬细胞的分化。 RHS2可以抑制DC的成熟以及CD80、CD86和MHCII的表达。分泌IFN-γ、IL-2和TNF-α的CD3+CD4+和CD3+CD8+T细胞数量减少,分泌IL-4的CD3+CD4+T细胞数量增加,表明RHS2可以抑制CD4T细胞和CD8T细胞的活化,从而抑制Th1免疫反应。 RHS2 抑制细胞毒性 T 淋巴细胞对靶细胞的清除。用RHS2和OVA免疫小鼠后,血清IgG2b显着降低,IgM升高。结果表明RHS2对宿主免疫反应具有抑制作用。蜱虫已经进化出多种方式来规避适应性免疫。它们的丝氨酸蛋白酶抑制剂抑制 BMDC 分化以减少免疫反应。
Rhipicephalus haemaphysaloides is a widespread tick species in China and other South East Asian countries, where it is the vector of many pathogens. The objective of this study was to study the role of serpin (serine protease inhibitor) during the tick-host interaction. The differentiation of bone marrow-derived dendritic cells (BMDC) was induced in vitro, and the effect of RHS2 on the maturation of DCs was evaluated. The effects of RHS2 on T cell activation and cytotoxic T lymphocytes’ (CTLs) activity were analyzed by flow cytometry. Antibody subtypes after immunization of mice with RHS2 and OVA were determined. RHS2 can inhibit the differentiation of bone marrow-derived cells into DCs and promote their differentiation into macrophages. RHS2 can inhibit the maturation of DCs and the expression of CD80, CD86 and MHCII. The number of CD3+CD4+ and CD3+CD8+ T cells secreting IFN-γ, IL-2 and TNF-α was decreased, and the number of CD3+CD4+ T cells secreting IL-4 was increased, indicating that RHS2 can inhibit the activation of CD4 T cells and CD8 T cells, leading to inhibition of Th1 immune response. RHS2 inhibits the elimination of target cells by cytotoxic T lymphocytes. After immunization of mice with RHS2 and OVA, serum IgG2b was significantly reduced and IgM was increased. The results show that RHS2 has an inhibitory effect on the host immune response. Ticks have evolved various ways to circumvent adaptive immunity. Their serpin inhibits BMDC differentiation to reduce immune responses.
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