南方医院陈烨:具核梭杆菌分泌胞外囊泡以破坏肠屏障
创作:王新宇 审核:aluba 04月13日
  • FnEV促进巨噬细胞的氧化应激,并诱导巨噬细胞向促炎表型的M1巨噬细胞极化;
  • 在巨噬细胞/Caco-2(结肠上皮细胞系)共培养中,FnEV通过激活Caco-2细胞的RIPK1及RIPK3并促进其聚集形成坏死小体,以诱导坏死性凋亡,从而促进肠道上皮屏障受损及氧化应激损伤;
  • TNF-α中和抗体或RIPK1抑制剂逆转FnEV诱导的上述变化;
  • 在DSS诱导的小鼠结肠炎模型中,FnEV通过RIPK1介导的凋亡破坏肠道上皮屏障功能,过继转移FnEV预处理的巨噬细胞有相似作用。
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aluba
具核梭杆菌(Fn)分泌的胞外囊泡(FnEV)携带多种有害分子,影响肠道中的菌群-宿主互作,尤其是溃疡性结肠炎(UC)中的上皮稳态。南方医科大学南方医院的陈烨团队在Gut Microbes上发表的一项最新研究,发现在细胞系及小鼠模型中,FnEV均可通过促进巨噬细胞的M1极化,并通过激活FADD-RIPK1-caspase 3信号通路以促进肠道上皮细胞的坏死性凋亡,从而破坏肠道上皮屏障。
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Gut Microbes [IF:10.245]

Extracellular vesicles of Fusobacterium nucleatum compromise intestinal barrier through targeting RIPK1-mediated cell death pathway

具核梭杆菌胞外囊泡通过RIPK1介导的细胞死亡途径损伤肠道屏障功能

10.1080/19490976.2021.1902718

03-26, Article

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Microbial factors that mediate microbes-host interaction in ulcerative colitis (UC), a chronic disease seriously affecting human health, are not fully known. The emerging oncobacterium Fusobacterium nucleatum (Fn) secretes extracellular vesicles carrying several types of harmful molecules in the intestine which can alter microbes-host interaction, especially the epithelial homeostasis in UC. However, the mechanism is not yet clear. Previously, we isolated EVs by the ultracentrifugation of Fn culture media and characterized them as the potent inducer of pro-inflammatory cytokines. Here, we examined the mechanism in detail. We found that in macrophage/Caco-2 co-cultures, FnEVs significantly promoted epithelial barrier loss and oxidative stress damage, which are related to epithelial necroptosis caused by the activation of receptor-interacting protein kinase 1 (RIPK1) and receptor-interacting protein kinase 3 (RIPK3). Furthermore, FnEVs promoted the migration of RIPK1 and RIPK3 into necrosome in Caco2 cells. Notably, these effects were reversed by TNF-α neutralizing antibody or Necrostatin-1 (Nec-1), a RIPK1 inhibitor. This suggested that FADD-RIPK1-caspase-3 signaling is involved in the process. Moreover, the observed effects were verified in the murine colitis model treated with FnEVs or by adoptive transfer of FnEVs-trained macrophages. In conclusion, we propose that RIPK1-mediated epithelial cell death promotes FnEVs-induced gut barrier disruption in UC and the findings can be used as the basis to further investigate this disease.

First Authors:
Le Liu,Liping Liang

Correspondence Authors:
Ye Chen

All Authors:
Le Liu,Liping Liang,Chenghai Yang,Youlian Zhou,Ye Chen

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