Immunotherapies for urinary tract infection

Urinary tract infections are a common cause of bacterial infection, especially in females. These infections are often chronic or recurrent and can cause long-term damage to the urinary tract, especially in children. In some cases, the bacteria can ascend to the kidney and cause kidney scarring, a pivotal precursor to the development of chronic kidney disease, which predisposes to systemic health complications, including cardiovascular disease and diabetes. The most common cause of urinary tract infection is uropathogenic Escherichia coli, which accounts for >80% of infections. Importantly, this pathogen is becoming increasingly resistant to existing antibiotic therapies. Therefore, there is an unmet need for alternative strategies to treat these infections and prevent deleterious sequelae in susceptible individuals. Our approach involves targeting the host immune system rather than the bacteria, which we propose will reduce the burden of the bacterial infection and limit the severity of the associated renal complications. Our idea is to therapeutically target specific immune cytokines to protect against bacterial infections in the urinary tract. We have established a complete toolbox of genetically modified mice, translational in vivo infection models, human patients and analysis platforms to enable us to determine the role of cytokines in urinary tract infection. We aim to use these established tools to provide crucial evidence for re-purposing emerging immunotherapies developed for other diseases. This is likely to provide a much-needed alternative therapy to antibiotics to combat the bacterial resistance in urinary tract infections, promote tissue repair to limit the severity of renal complications and reduce the likelihood of progression to chronic kidney disease.