Epithelial C5aR1 Signaling Enhances Uropathogenic Escherichia coli Adhesion to Human Renal Tubular Epithelial Cells
Recent work in a murine model of ascending urinary tract infection has suggested that C5a/C5aR1 interactions play a pathogenic role in the development of renal infection through enhancement of bacterial adhesion/colonization to renal tubular epithelial cells (RTECs). In the present study, we extende...
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2018-05-01
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doaj-b25d9368b9354b44b1f8d32ecc008d252020-11-24T22:33:50ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-05-01910.3389/fimmu.2018.00949370805Epithelial C5aR1 Signaling Enhances Uropathogenic Escherichia coli Adhesion to Human Renal Tubular Epithelial CellsYun Song0Kun-Yi Wu1Weiju Wu2Zhao-Yang Duan3Ya-Feng Gao4Liang-Dong Zhang5Tie Chong6Malgorzata A. Garstka7Wuding Zhou8Ke Li9Core Research Laboratory, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaCore Research Laboratory, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaMedical Research Council (MRC) Centre for Transplantation, King’s College London, Guy’s Hospital, London, United KingdomDepartment of Nephrology, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaCore Research Laboratory, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Urology, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Urology, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaCore Research Laboratory, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaMedical Research Council (MRC) Centre for Transplantation, King’s College London, Guy’s Hospital, London, United KingdomCore Research Laboratory, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaRecent work in a murine model of ascending urinary tract infection has suggested that C5a/C5aR1 interactions play a pathogenic role in the development of renal infection through enhancement of bacterial adhesion/colonization to renal tubular epithelial cells (RTECs). In the present study, we extended these observations to human. We show that renal tubular epithelial C5aR1 signaling is involved in promoting uropathogenic Escherichia coli (UPEC) adhesion/invasion of host cells. Stimulation of primary cultures of RTEC with C5a resulted in significant increases in UPEC adhesion/invasion of the RTEC. This was associated with enhanced expression of terminal α-mannosyl residues (Man) (a ligand for type 1 fimbriae of E. coli) in the RTEC following C5a stimulation. Mechanism studies revealed that C5aR1-mediated activation of ERK1/2/NF-κB and upregulation of proinflammatory cytokine production (i.e., TNF-α) is at least partly responsible for the upregulation of Man expression and bacterial adhesion. Clinical sample studies showed that C5aR1 and Man were clearly detected in the renal tubular epithelium of normal human kidney biopsies, and UPEC bound to the epithelium in a d-mannose-dependent manner. Additionally, C5a levels were significantly increased in urine of urinary tract infection patients compared with healthy controls. Our data therefore demonstrate that, in agreement with observations in mice, human renal tubular epithelial C5aR1 signaling can upregulate Man expression in RTEC, which enhances UPEC adhesion to and invasion of RTEC. It also suggests the in vivo relevance of upregulation of Man expression in renal tubular epithelium by C5a/C5aR1 interactions and its potential impact on renal infection.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00949/fullC5aR1uropathogenic Escherichia colirenal tubular epithelial cellbacterial adhesion/invasionmannosyl residues |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yun Song Kun-Yi Wu Weiju Wu Zhao-Yang Duan Ya-Feng Gao Liang-Dong Zhang Tie Chong Malgorzata A. Garstka Wuding Zhou Ke Li |
spellingShingle |
Yun Song Kun-Yi Wu Weiju Wu Zhao-Yang Duan Ya-Feng Gao Liang-Dong Zhang Tie Chong Malgorzata A. Garstka Wuding Zhou Ke Li Epithelial C5aR1 Signaling Enhances Uropathogenic Escherichia coli Adhesion to Human Renal Tubular Epithelial Cells Frontiers in Immunology C5aR1 uropathogenic Escherichia coli renal tubular epithelial cell bacterial adhesion/invasion mannosyl residues |
author_facet |
Yun Song Kun-Yi Wu Weiju Wu Zhao-Yang Duan Ya-Feng Gao Liang-Dong Zhang Tie Chong Malgorzata A. Garstka Wuding Zhou Ke Li |
author_sort |
Yun Song |
title |
Epithelial C5aR1 Signaling Enhances Uropathogenic Escherichia coli Adhesion to Human Renal Tubular Epithelial Cells |
title_short |
Epithelial C5aR1 Signaling Enhances Uropathogenic Escherichia coli Adhesion to Human Renal Tubular Epithelial Cells |
title_full |
Epithelial C5aR1 Signaling Enhances Uropathogenic Escherichia coli Adhesion to Human Renal Tubular Epithelial Cells |
title_fullStr |
Epithelial C5aR1 Signaling Enhances Uropathogenic Escherichia coli Adhesion to Human Renal Tubular Epithelial Cells |
title_full_unstemmed |
Epithelial C5aR1 Signaling Enhances Uropathogenic Escherichia coli Adhesion to Human Renal Tubular Epithelial Cells |
title_sort |
epithelial c5ar1 signaling enhances uropathogenic escherichia coli adhesion to human renal tubular epithelial cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-05-01 |
description |
Recent work in a murine model of ascending urinary tract infection has suggested that C5a/C5aR1 interactions play a pathogenic role in the development of renal infection through enhancement of bacterial adhesion/colonization to renal tubular epithelial cells (RTECs). In the present study, we extended these observations to human. We show that renal tubular epithelial C5aR1 signaling is involved in promoting uropathogenic Escherichia coli (UPEC) adhesion/invasion of host cells. Stimulation of primary cultures of RTEC with C5a resulted in significant increases in UPEC adhesion/invasion of the RTEC. This was associated with enhanced expression of terminal α-mannosyl residues (Man) (a ligand for type 1 fimbriae of E. coli) in the RTEC following C5a stimulation. Mechanism studies revealed that C5aR1-mediated activation of ERK1/2/NF-κB and upregulation of proinflammatory cytokine production (i.e., TNF-α) is at least partly responsible for the upregulation of Man expression and bacterial adhesion. Clinical sample studies showed that C5aR1 and Man were clearly detected in the renal tubular epithelium of normal human kidney biopsies, and UPEC bound to the epithelium in a d-mannose-dependent manner. Additionally, C5a levels were significantly increased in urine of urinary tract infection patients compared with healthy controls. Our data therefore demonstrate that, in agreement with observations in mice, human renal tubular epithelial C5aR1 signaling can upregulate Man expression in RTEC, which enhances UPEC adhesion to and invasion of RTEC. It also suggests the in vivo relevance of upregulation of Man expression in renal tubular epithelium by C5a/C5aR1 interactions and its potential impact on renal infection. |
topic |
C5aR1 uropathogenic Escherichia coli renal tubular epithelial cell bacterial adhesion/invasion mannosyl residues |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2018.00949/full |
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