Related Experiment Video
Updated: Mar 16, 2026
Establishment and Characterization of UTI and CAUTI in a Mouse Model
Published on: June 23, 2015
Never make assumptions: the complicated role of complement in urinary tract infections
Joshua M Thurman1, Raphael A Nemenoff1
1Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA.
Insights
Blocking C5a receptor 1 (C5aR1) reduced kidney scarring during a urinary tract infection in mice. Surprisingly, this complement inhibition also enhanced bacterial clearance, suggesting unexpected benefits of targeting the complement system.
Area of Science:
- Immunology
- Nephrology
- Microbiology
Background:
- Complement activation contributes to inflammation and tissue damage in diseases.
- Complement-inhibitory drugs are used for inflammatory conditions.
- Inhibiting the complement system may increase infection risk.
Purpose of the Study:
- To investigate the role of C5a receptor 1 (C5aR1) in renal fibrosis during urinary tract infections.
- To determine the effect of C5aR1 blockade on bacterial clearance and infection resolution.
Main Methods:
- Utilized a mouse model of urinary tract infection with Escherichia coli.
- Administered C5aR1 blockade to assess its impact on renal fibrosis and infection.
Main Results:
- C5aR1 blockade significantly reduced renal fibrosis.
- Surprisingly, C5aR1 blockade accelerated the clearance of Escherichia coli infection.
- C5a, a pro-inflammatory molecule, was found to impair macrophage-mediated bacterial killing.
Conclusions:
- Targeting C5aR1 offers a potential therapeutic strategy for reducing renal fibrosis in urinary tract infections.
- Complement inhibition via C5aR1 blockade may unexpectedly enhance bacterial clearance.
- The complement cascade has complex roles, including potentially hindering pathogen elimination by immune cells.
Abstract:
Complement activation can cause tissue inflammation and injury, and complement-inhibitory drugs are effective treatments for several inflammatory diseases. The complement cascade is part of the body's defense against bacteria and other pathogens, however, and a major concern regarding inhibition of this system is that it may increase the risk for infection. Now, a study by Choudhry et al. demonstrates that blockade of signaling at one of the C5a receptors (C5a receptor 1 [C5aR1]) reduces renal fibrosis in a mouse model of urinary tract infection with Escherichia coli. Surprisingly, C5aR1 blockade was also associated with faster clearance of the infection. The results of this study demonstrate that C5a-a highly proinflammatory molecule-reduces bacterial killing by macrophages. Other recent studies have also shown that C5a impairs the elimination of tumor cells by the immune system. These data indicate that complement inhibition may have some unexpected benefits. These results also demonstrate, however, that the complement cascade probably has physiologic functions that have yet to be discovered.
More Related Videos
07:34Isolation of Single Intracellular Bacterial Communities Generated from a Murine Model of Urinary Tract Infection for Downstream Single-cell Analysis
Published on: April 16, 2019
10:23Urinary Tract Infection in a Small Animal Model: Transurethral Catheterization of Male and Female Mice
Published on: December 1, 2017
Related Concept Videos
01:27Complement System
01:25Urinary Tract Infection II: Pathophysiology
01:26Urinary Tract Infection I: Introduction
01:26Urine Studies II: Urine Culture and Sensitivity Test
01:30Urinary Tract Infection III: Diagnostic Studies and Interprofessional Care
01:23Antimicrobial Proteins
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...