Amblyomma sculptum Salivary PGE2 Modulates the Dendritic Cell-Rickettsia rickettsii Interactions in vitro and in vivo
Amblyomma sculptum Salivary PGE2 Modulates the Dendritic Cell-Rickettsia rickettsii Interactions in vitro and in vivo
复制标题
DOI：
10.3389/fimmu.2019.00118
复制
发表时间：
2019-02-04
影响因子：
7.3
通讯作者：
Sa-Nunes, Anderson
中科院分区：
文献类型：
--
作者：
Esteves, Eliane;Bizzarro, Bruna;Sa-Nunes, Anderson
雕刻钝眼蜱是立克次体的重要传播媒介，立克次体是落基山斑疹热的病原体，也是影响人类的最致命的蜱传病原体。为了吸食脊椎动物宿主的血液，A。雕塑瘤分泌唾液混合物，其可与皮肤驻留树突状细胞（DC）相互作用并调节其功能。本工作旨在描述A.雕塑唾液-宿主DC网络和参与该界面的免疫调节组分的生物化学性质。a.雕塑唾液抑制LPS刺激的鼠DC产生炎性细胞因子。通过反相色谱法分离低分子量唾液内容物，发现从49 - 55%乙腈梯度洗脱的活性级分。先前的研究表明，这种洗脱模式与前列腺素E-2（PGE（2））的观察结果相匹配，并且这种脂质介质的分子身份已通过新的高分辨率质谱法明确证实。用R.首次证实了立克次氏体导致促炎细胞因子的产生，而促炎细胞因子的产生被A.雕塑唾液和PGE（2），也用人DC实现的结果。小鼠树突状细胞的过继转移与R。立克次氏体，然后用A.雕塑唾液或PGE（2）没有改变与细胞回忆反应相关的细胞因子谱，而这些小鼠血清中的IgG 2a特异性抗体减少。总之，这些发现强调了PGE（2）作为蜱唾液的通用免疫调节剂的作用。此外，它有助于新的方法来探索R。立克次氏体-DC相互作用在体外和体内。
Amblyomma sculptum is an important vector of Rickettsia rickettsii, causative agent of Rocky Mountain spotted fever and the most lethal tick-borne pathogen affecting humans. To feed on the vertebrate host's blood, A. sculptum secretes a salivary mixture, which may interact with skin resident dendritic cells (DCs) and modulate their function. The present work was aimed at depicting the A. sculptum saliva-host DC network and the biochemical nature of the immunomodulatory component(s) involved in this interface. A. sculptum saliva inhibits the production of inflammatory cytokines by murine DCs stimulated with LPS. The fractionation of the low molecular weight salivary content by reversed-phase chromatography revealed active fractions eluting from 49 to 55% of the acetonitrile gradient. Previous studies suggested that this pattern of elution matches with that observed for prostaglandin E-2 (PGE(2)) and the molecular identity of this lipid mediator was unambiguously confirmed by a new high-resolution mass spectrometry methodology. A productive infection of murine DCs by R. rickettsii was demonstrated for the first time leading to proinflammatory cytokine production that was inhibited by both A. sculptum saliva and PGE(2), a result also achieved with human DCs. The adoptive transfer of murine DCs incubated with R. rickettsii followed by treatment with A. sculptum saliva or PGE(2) did not change the cytokine profile associated to cellular recall responses while IgG2a-specific antibodies were decreased in the serum of these mice. Together, these findings emphasize the role of PGE(2) as a universal immunomodulator of tick saliva. In addition, it contributes to new approaches to explore R. rickettsii-DC interactions both in vitro and in vivo.