Complicated urinary tract infection is associated with uroepithelial expression of proinflammatory protein S100A8
Leticia Reyes1, Sophie Alvarez, Ayman Allam
1University of Florida, College of Veterinary Medicine, Department of Infectious Diseases & Pathology, P.O. Box 110880, Gainesville, FL 32611-0880, USA. lreyes@ufl.edu
Abstract:
F344 rats chronically infected with Ureaplasma parvum develop two distinct profiles: asymptomatic urinary tract infection (UTI) and UTI complicated by struvite urolithiasis. To identify factors that affect disease outcome, we characterized the temporal host immune response during infection by histopathologic analysis and in situ localization of U. parvum. We also used differential quantitative proteomics to identify distinguishing host cellular responses associated with complicated UTI. In animals in which microbial colonization was limited to the mucosal surface, inflammation was indistinguishable from that which occurred in sham-inoculated controls, and the inflammation resolved by 72 h postinoculation (p.i.) in both groups. However, inflammation persisted in animals with microbial colonization that extended into the deeper layers of the submucosa. Proteome profiling showed that bladder tissues from animals with complicated UTIs had significant increases (P < 0.01) in proteins involved in apoptosis, oxidative stress, and inflammation. Animals with complicated UTIs (2 weeks p.i.) had the highest concentrations of the proinflammatory protein S100A8 (P
Insights
Invasive Ureaplasma parvum colonization triggers chronic inflammation and immune dysregulation, leading to complicated urinary tract infections (UTIs) and struvite urolithiasis in rats. Asymptomatic UTIs show limited inflammation.
Area of Science:
- Microbiology
- Immunology
- Urology
Background:
- Ureaplasma parvum infection in F344 rats can lead to either asymptomatic urinary tract infections (UTIs) or complicated UTIs with struvite urolithiasis.
- Understanding the host immune response is crucial for differentiating disease outcomes.
Purpose of the Study:
- To investigate the temporal host immune response to Ureaplasma parvum infection.
- To identify host cellular responses distinguishing complicated UTIs from asymptomatic infections using differential quantitative proteomics.
Main Methods:
- Histopathologic analysis and in situ localization of U. parvum.
- Differential quantitative proteomics of bladder tissues.
- Correlation analysis of protein and cytokine levels.
Main Results:
- Persistent inflammation was observed in animals with invasive submucosal colonization, unlike resolved inflammation in asymptomatic cases.
- Complicated UTIs showed increased proteins related to apoptosis, oxidative stress, and inflammation.
- Elevated S100A8 protein in bladder tissue correlated with pro-inflammatory cytokines in urine, originating from the uroepithelium.
Conclusions:
- Invasive Ureaplasma parvum colonization of the bladder triggers chronic inflammation and immune dysregulation.
- This immune dysregulation is potentially critical for the development of struvite formation in complicated UTIs.
Related Concept Videos
Urinary Tract Infection II: Pathophysiology
Urinary Tract Infection I: Introduction
Urinary Tract Infection III: Diagnostic Studies and Interprofessional Care
Acute Pyelonephritis I: Introduction
Urine Studies II: Urine Culture and Sensitivity Test
Microbiota of the Urogenital Tract


