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Alpha-hemolysin of uropathogenic Escherichia coli induces GM-CSF-mediated acute kidney injury
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 induc...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914670/ https://www.ncbi.nlm.nih.gov/pubmed/31719643 http://dx.doi.org/10.1038/s41385-019-0225-6 |
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author | Wang, Changying Li, Qianqian Lv, Junqiang Sun, Xuan Cao, Yang Yu, Kaiyuan Miao, Chunhui Zhang, Zhi-Song Yao, Zhi Wang, Quan |
author_facet | Wang, Changying Li, Qianqian Lv, Junqiang Sun, Xuan Cao, Yang Yu, Kaiyuan Miao, Chunhui Zhang, Zhi-Song Yao, Zhi Wang, Quan |
author_sort | Wang, Changying |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6914670 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-69146702019-12-20 Alpha-hemolysin of uropathogenic Escherichia coli induces GM-CSF-mediated acute kidney injury Wang, Changying Li, Qianqian Lv, Junqiang Sun, Xuan Cao, Yang Yu, Kaiyuan Miao, Chunhui Zhang, Zhi-Song Yao, Zhi Wang, Quan Mucosal Immunol Article 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. Nature Publishing Group US 2019-11-12 2020 /pmc/articles/PMC6914670/ /pubmed/31719643 http://dx.doi.org/10.1038/s41385-019-0225-6 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wang, Changying Li, Qianqian Lv, Junqiang Sun, Xuan Cao, Yang Yu, Kaiyuan Miao, Chunhui Zhang, Zhi-Song Yao, Zhi Wang, Quan Alpha-hemolysin of uropathogenic Escherichia coli induces GM-CSF-mediated acute kidney injury |
title | Alpha-hemolysin of uropathogenic Escherichia coli induces GM-CSF-mediated acute kidney injury |
title_full | Alpha-hemolysin of uropathogenic Escherichia coli induces GM-CSF-mediated acute kidney injury |
title_fullStr | Alpha-hemolysin of uropathogenic Escherichia coli induces GM-CSF-mediated acute kidney injury |
title_full_unstemmed | Alpha-hemolysin of uropathogenic Escherichia coli induces GM-CSF-mediated acute kidney injury |
title_short | Alpha-hemolysin of uropathogenic Escherichia coli induces GM-CSF-mediated acute kidney injury |
title_sort | alpha-hemolysin of uropathogenic escherichia coli induces gm-csf-mediated acute kidney injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914670/ https://www.ncbi.nlm.nih.gov/pubmed/31719643 http://dx.doi.org/10.1038/s41385-019-0225-6 |
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