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

作者：X. L. Li, Y. Liu, Yang Zou, Jiayun Zhang, Yugui Wang, Yingying Ding, Zhiqi Shi, Xiaola Guo, Shaohua Zhang, Hong Yin, Aijiang Guo, Shuai Wang · 发表于：Infection and Immunity · 年份：2024 · DOI：10.1128/iai.00232-24 · 被引用次数：8 · 研究领域：Parasitic infections in humans and animals、Parasites and Host Interactions、Parasitic Infections and Diagnostics

ABSTRACT 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 sum...