National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, China.
Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
BMC Immunol. 2018 Oct 24;19(1):29. doi: 10.1186/s12865-018-0267-7.
Excretory-secretory products released by Echinococcus granulosus protoscoleces (EgPSC-ESPs) are well-known to regulate T cell responses. However, their direct influence on the differentiation of B cell subsets remains largely elusive. This study investigated the effects of EgPSC-ESPs on the differentiation of IL-10-producing B cells (B10), and explored the possible role of Toll-like receptor 2 (TLR-2) signaling in this process.
In comparison to phosphate buffered saline (PBS), B cells exposed to the excretory-secretory products (ESPs) generated higher percentages of B10 cells, with higher expression of IL-10 mRNA, and larger amount of IL-10 production, which were in a dose dependent way. The mRNA and protein expression of TLR-2 in the ESPs-stimulated B cells were significantly higher than those in PBS, which was consistent to the results in B cells isolated from EgPSC infected mice. Moreover, TLR-2 B cells in response to ESPs stimulation expressed lower levels of IL-10 mRNA and produced undetectable IL-10 in comparison to those in normal B cells. In addition, Phosphatase and tensin homolog deleted on chromosome ten/AKT/Phosphatidylinositol-3 kinase (PTEN/AKT/PI3K) pathway was activated in ESPs-treated B cells, which was also dependent on TLR-2 signaling. Pam3CSK4, the agonist of TLR-2, could mock the effects of ESPs on the expression of PTEN, AKT and PI3K.
Overall, this study revealed that TLR-2 signaling was required for B10 induction mediated by EgPSC-ESPs, which might be an immunomodulatory target against the parasite infection.
细粒棘球蚴原头节分泌物（EgPSC-ESPs）中释放的排泄分泌产物（ESPs）被认为可以调节 T 细胞反应。然而，它们对 B 细胞亚群分化的直接影响在很大程度上仍不清楚。本研究调查了 EgPSC-ESPs 对产生白细胞介素 10 的 B 细胞（B10）分化的影响，并探讨了 Toll 样受体 2（TLR-2）信号在这一过程中的可能作用。
与磷酸盐缓冲液（PBS）相比，暴露于分泌产物（ESPs）的 B 细胞产生更高比例的 B10 细胞，IL-10 mRNA 表达更高，产生的 IL-10 量也更大，呈剂量依赖性。ESPs 刺激的 B 细胞中 TLR-2 的 mRNA 和蛋白表达明显高于 PBS，与从 EgPSC 感染小鼠分离的 B 细胞结果一致。此外，与正常 B 细胞相比，TLR-2 B 细胞对 ESPs 刺激的反应中 IL-10 mRNA 的表达水平较低，且产生的 IL-10 无法检测到。此外，ESP 处理的 B 细胞中磷酸酶和张力蛋白同源物缺失/蛋白激酶 B/磷脂酰肌醇-3 激酶（PTEN/AKT/PI3K）通路被激活，这也依赖于 TLR-2 信号。TLR-2 的激动剂 Pam3CSK4 可以模拟 ESPs 对 PTEN、AKT 和 PI3K 表达的影响。
总的来说，这项研究表明，TLR-2 信号通路是 EgPSC-ESPs 介导的 B10 诱导所必需的，这可能是针对寄生虫感染的一种免疫调节靶点。
