硬蜱丝氨酸蛋白酶抑制剂 RHS2 对宿主免疫反应的免疫调节作用。
Immunomodulatory effects of Rhipicephalus haemaphysaloides serpin RHS2 on host immune responses.
机构信息
Key Laboratory of Animal Parasitology of Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
出版信息
Parasit Vectors. 2019 Jul 11;12(1):341. doi: 10.1186/s13071-019-3607-4.
BACKGROUND
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.
METHODS
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.
RESULTS
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 CD3CD4 and CD3CD8 T cells secreting IFN-γ, IL-2 and TNF-α was decreased, and the number of CD3CD4 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.
CONCLUSIONS
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.
背景
血红扇头蜱是一种广泛分布于中国和其他东南亚国家的蜱种，是许多病原体的传播媒介。本研究旨在研究丝氨酸蛋白酶抑制剂（serpin）在蜱-宿主相互作用中的作用。
方法
在体外诱导骨髓来源树突状细胞（BMDC）的分化，并评估 RHS2 对 DC 成熟的影响。通过流式细胞术分析 RHS2 对 T 细胞激活和细胞毒性 T 淋巴细胞（CTL）活性的影响。用 RHS2 和 OVA 免疫小鼠后测定抗体亚型。
结果
RHS2 可抑制骨髓细胞向 DC 的分化，并促进其向巨噬细胞分化。RHS2 可抑制 DC 的成熟和 CD80、CD86 和 MHCII 的表达。分泌 IFN-γ、IL-2 和 TNF-α的 CD3CD4 和 CD3CD8 T 细胞数量减少，分泌 IL-4 的 CD3CD4 T 细胞数量增加，表明 RHS2 可抑制 CD4 T 细胞和 CD8 T 细胞的激活，导致 Th1 免疫应答受到抑制。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 显著降低，IgM 增加。
结论
结果表明，RHS2 对宿主免疫反应具有抑制作用。蜱已经进化出多种方法来规避适应性免疫。它们的丝氨酸蛋白酶抑制剂抑制 BMDC 分化，从而降低免疫反应。
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