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Intrarenal Injection of Escherichia coli in a Rat Model of Pyelonephritis
Published on: July 18, 2017
Protective role for C3aR in experimental chronic pyelonephritis
Shu-Juan Zhao1, Kun-Yi Wu1, Xiao-Yun Min1
1Core Research Laboratory, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
Insights
The complement component 3a receptor (C3aR) protects against chronic kidney infection. Activating C3aR may offer a new therapy for chronic pyelonephritis caused by E. coli.
Area of Science:
- Immunology
- Microbiology
- Nephrology
Background:
- The complement component 3a receptor (C3aR) is implicated in host defense and disease.
- Its role in chronic bacterial infections remains largely uncharacterized.
- Previous studies indicate C3aR is protective in acute bacterial infections.
Purpose of the Study:
- To investigate the role of C3aR in experimental chronic pyelonephritis.
- To determine if C3aR deficiency exacerbates kidney infection pathology.
- To explore the therapeutic potential of C3aR modulation in chronic infection.
Main Methods:
- Utilized global C3aR deficient (C3ar-/-) and myeloid C3aR deficient (Lyz2-C3ar-/-) mice.
- Infected mice with uropathogenic E. coli (UPEC) strain IH11128.
- Assessed renal bacterial load, histological lesions, apoptosis, inflammation, and extracellular matrix deposition.
- Evaluated macrophage phagocytosis of UPEC.
- Administered a C3aR agonist to assess therapeutic effects.
Main Results:
- C3aR deficiency led to increased renal bacterial load, exacerbated histological damage, and heightened inflammation and matrix deposition.
- Myeloid C3aR played a significant role in C3aR-mediated protection.
- C3aR-/- macrophages showed impaired UPEC phagocytosis.
- C3aR agonist treatment reduced disease severity in experimental chronic pyelonephritis.
Conclusions:
- C3aR is protective against experimental chronic pyelonephritis.
- Macrophage C3aR is crucial for this protective effect.
- C3aR is essential for macrophage phagocytosis of UPEC.
- C3aR activation presents a potential therapeutic strategy for chronic infections.
Abstract:
Emerging evidence suggest that C3aR plays important roles in homeostasis, host defense and disease. Although it is known that C3aR is protective in several models of acute bacterial infections, the role for C3aR in chronic infection is largely unknown. Here we show that C3aR is protective in experimental chronic pyelonephritis. Global C3aR deficient (C3ar-/- ) mice had higher renal bacterial load, more pronounced renal histological lesions, increased renal apoptotic cell accumulation, tissue inflammation and extracellular matrix deposition following renal infection with uropathogenic E. coli (UPEC) strain IH11128, compared to WT control mice. Myeloid C3aR deficient (Lyz2-C3ar-/- ) mice exhibited a similar disease phenotype to global C3ar-/- mice. Pharmacological treatment with a C3aR agonist reduced disease severity in experimental chronic pyelonephritis. Furthermore, macrophages of C3ar-/- mice exhibited impaired ability to phagocytose UPEC. Our data clearly demonstrate a protective role for C3aR against experimental chronic pyelonephritis, macrophage C3aR plays a major role in the protection, and C3aR is necessary for phagocytosis of UPEC by macrophages. Our observation that C3aR agonist curtailed the pathology suggests a therapeutic potential for activation of C3aR in chronic infection.
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