Echinococcus multilocularis serpin regulates macrophage polarization and reduces gut dysbiosis in colitis

文献类型： 外文期刊

第一作者： Li, Xiaolu

作者： Li, Xiaolu;Liu, Yihui;Zou, Yang;Zhang, Jiayun;Wang, Yugui;Ding, Yingying;Shi, Zhiqi;Guo, Xiaola;Zhang, Shaohua;Yin, Hong;Guo, Aijiang;Wang, Shuai;Li, Xiaolu;Liu, Yihui;Zou, Yang;Zhang, Jiayun;Wang, Yugui;Ding, Yingying;Shi, Zhiqi;Guo, Xiaola;Zhang, Shaohua;Yin, Hong;Guo, Aijiang;Wang, Shuai;Yin, Hong;Guo, Aijiang;Wang, Shuai

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关键词： Echinococcus multilocularis serpin; inflammatory bowel disease; macrophages; gut microbiota

期刊名称：INFECTION AND IMMUNITY （ 影响因子：2.9； 五年影响因子：3.1 ）

ISSN： 0019-9567

年卷期： 2024 年 92 卷 8 期

页码：

收录情况： SCI

摘要： Helminths serve as principal regulators in modulating host immune responses, and their excretory-secretory proteins are recognized as potential therapeutic agents for inflammatory bowel disease. Nevertheless, our comprehension of the mechanisms underlying immunoregulation remains restricted. This investigation delves into the immunomodulatory role of a secretory protein serpin (Emu-serpin), within the larval stage of Echinococcus multilocularis. Our observations indicate that Emu-serpin effectively alleviates dextran sulfate sodium-induced colitis, yielding a substantial reduction in immunopathology and an augmentation of anti-inflammatory cytokines. Furthermore, this suppressive regulatory effect is concomitant with the reduction of gut microbiota dysbiosis linked to colitis, as evidenced by a marked impediment to the expansion of the pathobiont taxa Enterobacteriaceae. In vivo experiments demonstrate that Emu-serpin facilitates the expansion of M2 phenotype macrophages while concurrently diminishing M1 phenotype macrophages, alongside an elevation in anti-inflammatory cytokine levels. Subsequent in vitro investigations involving RAW264.7 and bone marrow macrophages reveal that Emu-serpin induces a conversion of M2 macrophage populations from a pro-inflammatory to an anti-inflammatory phenotype through direct inhibition. Adoptive transfer experiments reveal the peritoneal macrophages induced by Emu-serpin alleviate colitis and gut microbiota dysbiosis. In summary, these findings propose that Emu-serpin holds the potential to regulate macrophage polarization and maintain gut microbiota homeostasis in colitis, establishing it as a promising candidate for developing helminth therapy for preventing inflammatory diseases.

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