多棘球蚴血清素调节巨噬细胞极化并减轻结肠炎中的肠道菌群失调。

IF 2.9 3区 医学 Q3 IMMUNOLOGY
Infection and Immunity Pub Date : 2024-08-13 Epub Date: 2024-07-22 DOI:10.1128/iai.00232-24
Xiaolu Li, Yihui Liu, Yang Zou, Jiayun Zhang, Yugui Wang, Yingying Ding, Zhiqi Shi, Xiaola Guo, Shaohua Zhang, Hong Yin, Aijiang Guo, Shuai Wang
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引用次数: 0

摘要

蠕虫是调节宿主免疫反应的主要调节剂,其排泄分泌蛋白被认为是治疗炎症性肠病的潜在药物。然而,我们对免疫调节机制的了解仍然有限。这项研究深入探讨了分泌蛋白丝蛋白(Emu-serpin)在多棘球蚴幼虫阶段的免疫调节作用。我们的观察结果表明,Emu-serpin 能有效缓解葡聚糖硫酸钠诱导的结肠炎,大幅减少免疫病理反应,增加抗炎细胞因子。此外,这种抑制性调节作用还能同时减轻与结肠炎有关的肠道微生物群失调,病原菌类群肠杆菌科的扩张受到明显阻碍就是证明。体内实验表明,Emu-serpin 可促进 M2 表型巨噬细胞的扩张,同时减少 M1 表型巨噬细胞,并提高抗炎细胞因子的水平。随后进行的涉及 RAW264.7 和骨髓巨噬细胞的体外研究表明,Emu-serpin 通过直接抑制作用诱导 M2 巨噬细胞群从促炎表型转变为抗炎表型。采纳转移实验显示,Emu-serpin诱导的腹腔巨噬细胞可缓解结肠炎和肠道微生物群失调。总之,这些研究结果表明,Emu-serpin 具有调节巨噬细胞极化和维持结肠炎中肠道微生物群平衡的潜力,使其成为开发螺旋体疗法以预防炎症性疾病的有希望的候选物质。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Echinococcus multilocularis serpin regulates macrophage polarization and reduces gut dysbiosis in colitis.

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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来源期刊
Infection and Immunity
Infection and Immunity 医学-传染病学
CiteScore
6.00
自引率
6.50%
发文量
268
审稿时长
3 months
期刊介绍: Infection and Immunity (IAI) provides new insights into the interactions between bacterial, fungal and parasitic pathogens and their hosts. Specific areas of interest include mechanisms of molecular pathogenesis, virulence factors, cellular microbiology, experimental models of infection, host resistance or susceptibility, and the generation of innate and adaptive immune responses. IAI also welcomes studies of the microbiome relating to host-pathogen interactions.
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