Reg4 and complement factor D prevent the overgrowth of E. coli in the mouse gut

Reg4 and complement factor D prevent the overgrowth of E. coli in the mouse gut
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Reg4 和补体因子 D 可防止小鼠肠道中大肠杆菌过度生长

DOI:
10.1038/s42003-020-01219-2
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发表时间:
2020-09-02
影响因子:
5.9
通讯作者:
Yang, Rongcun
Yang, Rongcun
中科院分区:
生物学2区
文献类型:
--
作者:
Qi, Houbao;Wei, Jianmei;Yang, Rongcun

文献摘要

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肠杆菌科(如大肠杆菌)的扩张是肠道炎症的一个主要特征,且与多种人类疾病相关。然而,如何控制这些大肠杆菌的过度生长还不太清楚。在此,我们证明肠道补体因子D(CFD)在清除大肠杆菌方面起着重要作用。在CFD缺陷小鼠的肠道中发现大肠杆菌增多,这些大肠杆菌可刺激炎性巨噬细胞诱发结肠炎。我们还表明,在肠上皮细胞中表达的肠道Reg4可刺激补体介导的攻击复合物来清除大肠杆菌。Reg4缺陷小鼠体内大肠杆菌也增多。从小鼠结肠炎组织中分离出的优势大肠杆菌对CFD和Reg4介导的攻击复合物均敏感。因此,肠道Reg4和CFD介导的膜攻击复合物可能通过杀死炎性大肠杆菌来维持肠道内稳态。齐等人利用肠道特异性CFD缺失小鼠表明肠道补体因子D(CFD)在清除大肠杆菌方面起着重要作用。他们发现从发炎肠道中分离出的大肠杆菌对CFD和Reg4介导的攻击复合物均敏感。这项研究为肠道中大肠杆菌水平如何保持在较低水平以防止肠道炎症提供了见解。
The expansion of Enterobacteriaceae, such as E. coli is a main characteristic of gut inflammation and is related to multiple human diseases. However, how to control these E. coli overgrowth is not well understood. Here, we demonstrate that gut complement factor D (CFD) plays an important role in eliminating E. coli. Increased E. coli, which could stimulate inflammatory macrophages to induce colitis, were found in the gut of CFD deficient mice. We also showed that gut Reg4, which is expressed in gut epithelial cells, stimulated complement-mediated attack complexes to eliminate E. coli. Reg4 deficient mice also had increased E. coli. The dominant E. coli were isolated from colitis tissues of mice and found to be sensitive to both CFD- and Reg4-mediated attack complexes. Thus, gut Reg4- and CFD-mediated membrane attack complexes may maintain gut homeostasis by killing inflammatory E. coli. Qi et al. show that gut complement factor D (CFD) plays an important role in eliminating Escherichia coli, using gut specific CFD null mice. They find that E. coli isolated from inflamed guts are sensitive to both CFD and Reg4-mediated attack complexes. This study provides insights into how the level of E. Coli is kept low in the gut to prevent its inflammation.