Epithelial C5aR1 Signaling Enhances Uropathogenic Escherichia coli Adhesion to Human Renal Tubular Epithelial Cells

Frontiers in Immunology
Yun SongKe Li

Abstract

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 significa...Continue Reading

References

Aug 1, 1991·The Journal of Clinical Investigation·R A BrooimansM R Daha
Aug 10, 2000·Clinical and Experimental Immunology·R ZahediA E Davis
May 16, 2002·Molecular Microbiology·Chia-Suei HungScott J Hultgren
May 25, 2002·Cellular Microbiology·Matthew A Mulvey
Jul 5, 2003·Science·Gregory G AndersonScott J Hultgren
Jul 10, 2003·Infectious Disease Clinics of North America·Björn WulltC Svanborg
Aug 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ke LiNeil S Sheerin
Aug 30, 2008·Journal of the American Society of Nephrology : JASN·Faikah GuelerNelli Shushakova
Nov 18, 2009·Infection and Immunity·Kelsey E Sivick, Harry L T Mobley
Aug 15, 2012·Journal of Diabetes and Its Complications·Ishan HirjiAndres Gomez-Caminero
Apr 30, 2013·Transplantation Proceedings·O AkT Demir
Aug 1, 2013·Journal of the American Heart Association·David W ScottRakesh P Patel
Oct 29, 2013·Seminars in Nephrology·James W McCulloughJoshua M Thurman
Feb 4, 2014·Infectious Disease Clinics of North America·Betsy Foxman
Apr 9, 2015·Nature Reviews. Microbiology·Ana L Flores-MirelesScott J Hultgren
Jun 11, 2017·Molecular Immunology·Yves LaumonnierJörg Köhl
Jan 24, 2018·Kidney International·Bi-Cheng LiuHui-Yao Lan

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Citations

Apr 7, 2019·Neurotoxicity Research·Laura BrandoliniSilvia Di Loreto

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Methods Mentioned

BETA
biopsies
ELISA
FCS
protein assay
fluorescence microscopy
Fluorescence
biopsy

Software Mentioned

Graphpad Prism
Image J

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