Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic; Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic, České Budějovice, Czech Republic.
Parasite Immunol. 2015 Feb;37(2):70-8. doi: 10.1111/pim.12162.
Type I interferon (IFN), mainly produced by dendritic cells (DCs), is critical in the host defence against tick-transmitted pathogens. Here, we report that salivary cysteine protease inhibitor from the hard tick Ixodes scapularis, sialostatin L2, affects IFN-β mediated immune reactions in mouse dendritic cells. Following IFN receptor ligation, the Janus activated kinases/signal transducer and activator of transcription (JAK/STAT) pathway is activated. We show that sialostatin L2 attenuates phosphorylation of STATs in spleen dendritic cells upon addition of recombinant IFN-β. LPS-stimulated dendritic cells release IFN-β which in turn leads to the induction of IFN-stimulated genes (ISG) through JAK/STAT pathway activation. The induction of two ISG, interferon regulatory factor 7 (IRF-7) and IP-10, was suppressed by sialostatin L2 in LPS-stimulated dendritic cells. Finally, the interference of sialostatin L2 with IFN action led to the enhanced replication of tick-borne encephalitis virus in DC. In summary, we present here that tick salivary cystatin negatively affects IFN-β responses which may consequently increase the pathogen load after transmission via tick saliva.
I 型干扰素（IFN）主要由树突状细胞（DCs）产生，在宿主防御蜱传播病原体中至关重要。在这里，我们报告硬蜱Ixodes scapularis 的唾液半胱氨酸蛋白酶抑制剂 sialostatin L2 影响小鼠树突状细胞中 IFN-β 介导的免疫反应。在 IFN 受体连接后，Janus 激活激酶/信号转导和转录激活因子（JAK/STAT）途径被激活。我们表明，sialostatin L2 可减弱重组 IFN-β 加入后脾树突状细胞中 STATs 的磷酸化。LPS 刺激的树突状细胞释放 IFN-β，反过来通过 JAK/STAT 途径的激活诱导 IFN 刺激基因（ISG）。两种 ISG，干扰素调节因子 7（IRF-7）和 IP-10 的诱导被 LPS 刺激的树突状细胞中的 sialostatin L2 抑制。最后，sialostatin L2 对 IFN 作用的干扰导致蜱传脑炎病毒在 DC 中的复制增强。总之，我们在这里提出，蜱唾液半胱氨酸蛋白酶抑制剂负调控 IFN-β 反应，这可能会增加蜱唾液传播后的病原体负荷。
