期刊
MUCOSAL IMMUNOLOGY
卷 13, 期 1, 页码 22-33出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41385-019-0225-6
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资金
- National Natural Science Foundation of China (NSFC) [31970133, 31670071, 81672740, 31700143]
- Intergovernmental international innovation cooperation [2018YFE0102000]
- Tianjin Science and Technology Commissioner Project [18JCZDJC36000]
- Science & Technology Development Fund of Tianjin Education Commission for Higher Education [2017ZD12]
- science foundation of Tianjin Medical University [2016KY2M08]
- National Key Technologies RD Program
Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections (UTIs), inducing acute pyelonephritis and may result in permanent renal scarring and failure. Alpha-hemolysin (HlyA), a key UPEC toxin, causes serious tissue damage; however, the mechanism through which HlyA induces kidney injury remains unclear. In the present study, granulocyte-macrophage colony-stimulating factor (GM-CSF) secreted by renal epithelial cells was upregulated by HlyA in vitro and in vivo, which induced M1 macrophage accumulation in kidney, and ADAM10 was found involved in HlyA-induced GM-CSF. Macrophage elimination or GM-CSF neutralization protected against acute kidney injury in mice, and increased GM-CSF was detected in urine of patients infected by hlyA-positive UPEC. In addition, HlyA was found to promote UPEC invasion into renal epithelial cells by interacting with Nectin-2 in vitro. However, HlyA did not affect bacterial titers during acute kidney infections, and HlyA-induced invasion did not contribute to GM-CSF upregulation in vitro, which indicate that HlyA-induced GM-CSF is independent of bacteria invasion. The role of GM-CSF in HlyA-mediated kidney injury may lead to novel strategies to treat acute pyelonephritis.
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