Schistosome eggs stimulate reactive oxygen species production to enhance M2 macrophage differentiation and promote hepatic pathology in schistosomiasis.
Schistosome eggs stimulate reactive oxygen species production to enhance M2 macrophage differentiation and promote hepatic pathology in schistosomiasis.
复制标题
血吸虫卵刺激活性氧的产生，增强 M2 巨噬细胞分化并促进血吸虫病的肝脏病理学
DOI：
10.1371/journal.pntd.0009696
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发表时间：
2021-08
影响因子：
3.8
通讯作者：
Su C
中科院分区：
文献类型：
--
作者：
Yu Y;Wang J;Wang X;Gu P;Lei Z;Tang R;Wei C;Xu L;Wang C;Chen Y;Pu Y;Qi X;Yu B;Chen X;Zhu J;Li Y;Zhang Z;Zhou S;Su C
血吸虫病是一种引起公共卫生关注的被忽视的热带疾病。日本血吸虫病和曼氏血吸虫病最具破坏性的病理变化主要是虫卵诱导的肉芽肿反应和继发性肝纤维化，可导致宿主门静脉高压甚至死亡。血吸虫卵诱导富含M2巨噬细胞的肉芽肿，这些M2巨噬细胞在肉芽肿的维持和随后的纤维化中起关键作用。活性氧（ROS），这是在感染过程中由刺激的巨噬细胞高度产生和M2巨噬细胞的分化所必需的，大量分布在肝脏中的沉积卵周围。然而，在S.日本血吸虫感染在此，我们观察到ROS在S.日本血吸虫感染小鼠。在感染小鼠中注射ROS抑制剂导致肝肉芽肿反应和纤维化减少。进一步的研究表明，抑制S.日本血吸虫感染的小鼠减少了M2的分化，伴随着M1巨噬细胞分化的增加。最后证明了S.日本血吸虫卵抗原（SEA）通过烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶2（NOX 2）和巨噬细胞线粒体诱导高水平ROS产生。我们的研究可能有助于更好地了解日本血吸虫病引起的肝脏病理机制，并有助于通过干扰ROS的产生来开发潜在的治疗策略。
Schistosomiasis is a neglected tropical disease of public health concern. The most devastating pathology in schistosomiasis japonica and mansoni is mainly attributed to the egg-induced granulomatous response and secondary fibrosis in host liver, which may lead to portal hypertension or even death of the host. Schistosome eggs induce M2 macrophages-rich granulomas and these M2 macrophages play critical roles in the maintenance of granuloma and subsequent fibrosis. Reactive oxygen species (ROS), which are highly produced by stimulated macrophages during infection and necessary for the differentiation of M2 macrophages, are massively distributed around deposited eggs in the liver. However, whether ROS are induced by schistosome eggs to subsequently promote M2 macrophage differentiation, and the possible underlying mechanisms as well, remain to be clarified during S. japonicum infection. Herein, we observed that extensive expression of ROS in the liver of S. japonicum-infected mice. Injection of ROS inhibitor in infected mice resulted in reduced hepatic granulomatous responses and fibrosis. Further investigations revealed that inhibition of ROS production in S. japonicum-infected mice reduces the differentiation of M2, accompanied by increased M1 macrophage differentiation. Finally, we proved that S. japonicum egg antigens (SEA) induce a high level of ROS production via both nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and mitochondria in macrophages. Our study may help to better understand the mechanism of schistosomiasis japonica-induced hepatic pathology and contribute to the development of potential therapeutic strategies by interfering with ROS production.
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