Tick sialostatins L and L2 differentially influence dendritic cell responses to Borrelia spirochetes.
Tick sialostatins L and L2 differentially influence dendritic cell responses to Borrelia spirochetes.
复制标题
DOI：
10.1186/s13071-015-0887-1
复制
发表时间：
2015-05-15
影响因子：
3.2
通讯作者：
Kopecký J
中科院分区：
文献类型：
--
作者：
Lieskovská J;Páleníková J;Langhansová H;Campos Chagas A;Calvo E;Kotsyfakis M;Kopecký J
蜱传播病原体在很大程度上是由蜱进食时释放的唾液支持的。树突状细胞（DC）作为免疫哨兵，并连接先天性和适应性免疫系统。它们控制免疫应答向Th 1或Th 2表型的极化。我们研究了来自硬蜱肩胛硬蜱的唾液半胱氨酸蛋白酶抑制剂，唾液酸抑制素L（Sialo L）和唾液酸抑制素L2（Sialo L2），是否影响暴露于伯氏疏螺旋体和相关Toll样受体配体的小鼠树突状细胞。在3 μM Sialo L和3 μM Sialo L2存在下，用疏螺旋体螺旋体或TLR配体活化通过GM-CSF或Flt-3配体从骨髓衍生的DC。ELISA法检测趋化因子和IFN-β的产生。使用特异性抗体通过蛋白质印迹法测试信号传导途径的激活。流式细胞仪检测DC表面CD 86的表达，确定DC的成熟程度。我们确定了半胱氨酸蛋白酶抑制剂对疏螺旋体感染的骨髓来源的DC中趋化因子的产生的影响。MIP-1α的产生被两种半胱氨酸蛋白酶抑制剂严重抑制，而IP-10仅被Sialo L2选择性抑制。由于TLR-2是由疏螺旋体螺旋体激活的主要受体，我们测试了半胱氨酸蛋白酶抑制剂是否影响由TLR-2配体脂磷壁酸（LTA）激活的信号传导途径。Sialo L2和弱Sialo L减弱细胞外基质调节激酶（Erk 1/2）途径。磷脂酰肌醇-3激酶（PI 3 K）/Akt通路和核因子-κB（NF-κB）的活化仅被Sialo L2降低。响应于伯氏疏螺旋体，Erk 1/2的激活被Sialo L2损害。在暴露于疏螺旋体、TLR-7和TLR-9配体的浆细胞样DC中分析IFN-β的产生。与Sialo L2相反，Sialo L降低了pDC中IFN-β的产生，并且还损害了这些细胞的成熟。这项研究表明，DC对疏螺旋体螺旋体的反应受到蜱半胱氨酸蛋白酶抑制剂的影响。Sialo L影响DC的成熟，从而影响适应性免疫应答。Sialo L2影响可能参与炎症反应发展的趋化因子的产生。半胱氨酸蛋白酶抑制剂对疏螺旋体生长在体内的影响进行了讨论。本文的在线版本（doi：10.1186/s13071-015-0887-1）包含补充材料，可供授权用户使用。
Transmission of pathogens by ticks is greatly supported by tick saliva released during feeding. Dendritic cells (DC) act as immunological sentinels and interconnect the innate and adaptive immune system. They control polarization of the immune response towards Th1 or Th2 phenotype. We investigated whether salivary cystatins from the hard tick Ixodes scapularis, sialostatin L (Sialo L) and sialostatin L2 (Sialo L2), influence mouse dendritic cells exposed to Borrelia burgdorferi and relevant Toll-like receptor ligands. DCs derived from bone-marrow by GM-CSF or Flt-3 ligand, were activated with Borrelia spirochetes or TLR ligands in the presence of 3 μM Sialo L and 3 μM Sialo L2. Produced chemokines and IFN-β were measured by ELISA test. The activation of signalling pathways was tested by western blotting using specific antibodies. The maturation of DC was determined by measuring the surface expression of CD86 by flow cytometry. We determined the effect of cystatins on the production of chemokines in Borrelia-infected bone-marrow derived DC. The production of MIP-1α was severely suppressed by both cystatins, while IP-10 was selectively inhibited only by Sialo L2. As TLR-2 is a major receptor activated by Borrelia spirochetes, we tested whether cystatins influence signalling pathways activated by TLR-2 ligand, lipoteichoic acid (LTA). Sialo L2 and weakly Sialo L attenuated the extracellular matrix-regulated kinase (Erk1/2) pathway. The activation of phosphatidylinositol-3 kinase (PI3K)/Akt pathway and nuclear factor-κB (NF-κB) was decreased only by Sialo L2. In response to Borrelia burgdorferi, the activation of Erk1/2 was impaired by Sialo L2. Production of IFN-β was analysed in plasmacytoid DC exposed to Borrelia, TLR-7, and TLR-9 ligands. Sialo L, in contrast to Sialo L2, decreased the production of IFN-β in pDC and also impaired the maturation of these cells. This study shows that DC responses to Borrelia spirochetes are affected by tick cystatins. Sialo L influences the maturation of DC thus having impact on adaptive immune response. Sialo L2 affects the production of chemokines potentially engaged in the development of inflammatory response. The impact of cystatins on Borrelia growth in vivo is discussed. The online version of this article (doi:10.1186/s13071-015-0887-1) contains supplementary material, which is available to authorized users.
登录
查看更多内容
I型Interferon自分泌 - 核酸环与树突状细胞的Toll样受体诱导的白介素-12p70分泌有关。
影响因子：
15.3
作者：
Gautier, G;Humbert, M;Deauvieau, F;Scuiller, M;Hiscott, J;Bates, EEM;Trinchieri, G;Caux, C;Garrone, P
通讯作者：
Garrone, P
DOI：
10.1073/pnas.1934678100
发表时间：
2003-09-16
影响因子：
11.1
作者：
Honda, K;Sakaguchi, S;Taniguchi, T
通讯作者：
Taniguchi, T
影响因子：
6.4
作者：
Cavassani, KA;Aliberti, JC;Ferreira, BR
通讯作者：
Ferreira, BR
影响因子：
4.8
作者：
Kotsyfakis, Michalis;Karim, Shahid;Ribeiro, Jose M. C.
通讯作者：
Ribeiro, Jose M. C.
影响因子：
4.8
作者：
Kotsyfakis, Michalis;Sa-Nunes, Anderson;Ribeiro, Jose M. C.
通讯作者：
Ribeiro, Jose M. C.