双胞胎 MIF通过CD74受体介导的NLRP3炎症酶激活诱导宿主肠道损伤
Mengge Chen1, Jianhua Li1, Xiaocen Wang1
1State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China.
PLoS neglected tropical diseases
|February 2, 2026
概括
巨十二 MIF (GdMIF) 通过CD74相互作用激活NLRP3炎症体,导致肠道损伤. 抑制这种途径可以减少炎症,并防止巨病.
科学领域:
- 免疫学 免疫学 免疫学
- 寄生虫学的寄生虫学
- 分子生物学分子生物学
背景情况:
- 十二指甲状腺通过腹引起全球公共卫生问题.
- 巨细胞迁移抑制因子 (MIF) 调解免疫反应;寄生虫衍生的MIF在疾病中的作用尚不清楚.
- 在巨病的发病过程中,G. duodenalis MIF (GdMIF) 的特定功能需要阐明.
研究的目的:
- 研究G. duodenalis MIF (GdMIF) 在激活CD74-NF-κB-NLRP3炎症酶通路中的作用.
- 为了确定GdMIF诱导的炎症酶激活在巨病期间对肠道损伤的影响.
- 探索GdMIF与宿主细胞受体的相互作用及其下游效应.
主要方法:
- 在体外和体内使用重组GdMIF (rGdMIF) 和感染G. duodenalis的子进行了体外和体内研究.
- 研究了NF-κB和NLRP3炎症酶的激活,GSDMD处理和细胞因子的释放.
- 使用共免疫沉 (Co-IP) 和双分子光补充 (BiFC) 验证了GdMIF与CD74的相互作用.
- 使用基因淘汰技术 (CD74,NF-κB) 和一种阻断GdMIF抗体.
主要成果:
- GdMIF是一种具有多巴胺相酶活性的外分蛋白质.
- GdMIF激活了NF-κB和NLRP3炎症酶,导致了热亡 (GSDMD处理,LDH和细胞因子释放).
- GdMIF直接与CD74受体发生相互作用.
- 抑制CD74或NF-κB抑制rGdMIF诱导的炎症酶激活和细胞因子的产生.
- 阻断GdMIF抗体减少了NLRP3的表达和肠道损伤在感染的小鼠.
- 抑制NLRP3可以缓解G. duodenalis引起的肠损伤.
结论:
- 通过CD74受体相互作用,GdMIF诱导NLRP3炎症酶激活和烧灭.
- 这种相互作用触发了亲炎性反应,导致病的肠损伤.
- 准GdMIF-CD74-NLRP3轴为巨病提供了一个潜在的治疗策略.
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