共生大肠杆菌对结肠上皮细胞恢复的有益作用与上皮细胞中的甲酰肽受体2（Fpr2）有关。
The beneficial effects of commensal E. coli for colon epithelial cell recovery are related with Formyl peptide receptor 2 (Fpr2) in epithelial cells.
作者信息
Chen Keqiang, McCulloch John, Das Neves Rodrigo, Rodrigues Gisele, Hsieh Wang-Ting, Gong Wanghua, Yoshimura Teizo, Huang Jiaqiang, O'hUigin Colm, Difilippantonio Simone, McCollum Matthew, Jones Georgette, Durum Scott K, Trinchieri Giorgio, Wang Ji Ming
机构信息
Laboratory of Cancer Innovation, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, 21702, USA.
Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA.
出版信息
Gut Pathog. 2023 Jun 15;15(1):28. doi: 10.1186/s13099-023-00557-w.
BACKGROUND
Formyl peptide receptor 2 (Fpr2) plays a crucial role in colon homeostasis and microbiota balance. Commensal E. coli is known to promote the regeneration of damaged colon epithelial cells. The aim of the study was to investigate the connection between E. coli and Fpr2 in the recovery of colon epithelial cells.
RESULTS
The deficiency of Fpr2 was associated with impaired integrity of the colon mucosa and an imbalance of microbiota, characterized by the enrichment of Proteobacteria in the colon. Two serotypes of E. coli, O22:H8 and O91:H21, were identified in the mouse colon through complete genome sequencing. E. coli O22:H8 was found to be prevalent in the gut of mice and exhibited lower virulence compared to O91:H21. Germ-free (GF) mice that were pre-orally inoculated with E. coli O22:H8 showed reduced susceptibility to chemically induced colitis, increased proliferation of epithelial cells, and improved mouse survival. Following infection with E. coli O22:H8, the expression of Fpr2 in colon epithelial cells was upregulated, and the products derived from E. coli O22:H8 induced migration and proliferation of colon epithelial cells through Fpr2. Fpr2 deficiency increased susceptibility to chemically induced colitis, delayed the repair of damaged colon epithelial cells, and heightened inflammatory responses. Additionally, the population of E. coli was observed to increase in the colons of Fpr2 mice with colitis.
CONCLUSION
Commensal E. coli O22:H8 stimulated the upregulation of Fpr2 expression in colon epithelial cells, and the products from E. coli induced migration and proliferation of colon epithelial cells through Fpr2. Fpr2 deficiency led to an increased E. coli population in the colon and delayed recovery of damaged colon epithelial cells in mice with colitis. Therefore, Fpr2 is essential for the effects of commensal E. coli on colon epithelial cell recovery.
背景
甲酰肽受体2（Fpr2）在结肠稳态和微生物群平衡中起关键作用。已知共生大肠杆菌可促进受损结肠上皮细胞的再生。本研究的目的是探讨大肠杆菌与Fpr2在结肠上皮细胞恢复中的联系。
结果
Fpr2的缺乏与结肠黏膜完整性受损和微生物群失衡有关，其特征是结肠中变形菌门富集。通过全基因组测序在小鼠结肠中鉴定出两种大肠杆菌血清型，O22:H8和O91:H21。发现大肠杆菌O22:H8在小鼠肠道中普遍存在，与O91:H21相比毒力较低。预先经口接种大肠杆菌O22:H8的无菌（GF）小鼠对化学诱导的结肠炎敏感性降低，上皮细胞增殖增加，小鼠存活率提高。感染大肠杆菌O22:H8后，结肠上皮细胞中Fpr2的表达上调，大肠杆菌O22:H8衍生的产物通过Fpr2诱导结肠上皮细胞迁移和增殖。Fpr2缺乏增加了对化学诱导结肠炎的易感性，延迟了受损结肠上皮细胞的修复，并加剧了炎症反应。此外，在患有结肠炎的Fpr2小鼠结肠中观察到大肠杆菌数量增加。
结论
共生大肠杆菌O22:H8刺激结肠上皮细胞中Fpr2表达上调，大肠杆菌产物通过Fpr2诱导结肠上皮细胞迁移和增殖。Fpr2缺乏导致结肠炎小鼠结肠中大肠杆菌数量增加，受损结肠上皮细胞恢复延迟。因此，Fpr2对于共生大肠杆菌对结肠上皮细胞恢复的作用至关重要。
Zotero 插件