Clonorchis sinensis calcium-binding protein Cs16 causes acute hepatic injury possibly by reprogramming the metabolic pathway of bone marrow-derived monocytes.
Clonorchis sinensis calcium-binding protein Cs16 causes acute hepatic injury possibly by reprogramming the metabolic pathway of bone marrow-derived monocytes.
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DOI：
10.3389/fcimb.2023.1280358
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发表时间：
2023
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
华支睾吸虫感染会导致肝脏和胆道系统的各种并发症，是东亚地区一种被忽视的热带疾病。在这项研究中，我们报道了中华茶树钙结合蛋白 Cs16 激活宿主免疫细胞并诱导肝脏免疫病理学。采用免疫组织化学方法检测Cs16在中华线虫成虫中的定位。采用ELISA法检测感染人和小鼠血清中抗Cs16 IgG抗体水平。使用胆管注射模型来阐明 Cs16 在体内的作用。 RT-qPCR 和 ELISA 用于检测 Cs16 处理的 BMM 体外细胞因子的产生。 Seahorse 实验用于检测 Cs16 处理的 BMM 的体外代谢途径。 Cs16 定位于中华栾树的外皮和肠道。感染中华线虫的人和小鼠表现出抗 Cs16 特异性抗体水平升高。利用胆管注射技术，我们发现Cs16在体内引起明显的炎症和肝坏死。 Cs16 治疗导致先天免疫细胞中炎症细胞因子的上调。此外，Cs16处理的单核细胞更依赖于糖酵解代谢途径。我们的研究结果表明，Cs16 是源自中华线虫成虫的潜在致病因子。通过重新编程先天免疫细胞的代谢途径，Cs16 触发肝脏中的促炎症反应，因此，Cs16 是预防和治疗华支睾吸虫病的潜在靶点。
Clonorchis sinensis infection results in various complications in the liver and biliary systems and is a neglected tropical disease in Eastern Asia. In this study, we report that C. sinensis calcium-binding protein Cs16 activates host immune cells and induces immunopathology in liver. Immunohistochemistry was used to detect the localization of Cs16 in C. sinensis adult worms. ELISA was used to detect the serum levels of anti-Cs16 IgG antibody in infected humans and mice. Bile duct injection model was used to figure out the role of Cs16 in vivo. RT-qPCR and ELISA were used to detect the cytokine production from Cs16-treated BMMs in vitro. Seahorse assay was used to detect the metabolic pathway of Cs16-treated BMMs in vitro. Cs16 localizes in the tegument and gut of C. sinensis. Humans and mice with C. sinensis infection exhibited increased levels of anti-Cs16-specific antibody. Using the bile duct injection technique, we found that Cs16 induced obvious inflammation and hepatic necrosis in vivo. Cs16 treatment caused the upregulation of inflammatory cytokines in innate immune cells. Moreover, Cs16-treated monocytes relied more on the glycolytic metabolic pathway. Our findings suggest that Cs16 is a potential pathogenic factor derived from C. sinensis adult worm. By reprogramming the metabolic pathway of innate immune cells, Cs16 triggers pro-inflammatory responses in the liver, and therefore, Cs16 is a potential target for the prevention and treatment of clonorchiasis.
日本血吸虫卵特异性蛋白 SjE16.7 招募中性粒细胞并诱导炎症性肝肉芽肿发生
影响因子：
3.8
作者：
Wu C;Chen Q;Fang Y;Wu J;Han Y;Wang Y;Yang Y;Chu M;Feng Y;Tan L;Guo X;Hu W;Wang Z
通讯作者：
Wang Z