Since a major complication of UTIs is frequent recurrence, there appears to be a fateful defect in the urinary immune system. A distinct feature of the bladder which appears to contribute to their susceptibility to reinfection is the high degree of atypical tissue remodeling that occurs following each infection, predisposing the bladder to future infections. Since very little is currently known regarding bladder remodeling, studies on this topic may reveal new strategies to combat recurrent UTIs. We have hypothesized that because of the highly cytotoxic and hyperosmolar nature of urine, the bladder initiates a vigorous re-epithelization and remodeling program to rapidly recover lost epithelium after each infection. Our preliminary studies have validated this notion and revealed that T cells recruited into the bladder are more specialized in directing tissue repair (Th2) than in pathogen elimination (Th1). Consequently, the infecting bacteria in the bladder are not completely eliminated following resolution of infection, predisposing this organ to future flare-ups. Since the tissue repair T cells recruited into the bladder tend to persist and could be quickly evoked with reinfection, the magnitude of the remodeling program is high, significantly impacting bladder voiding capacity. We have found that a critical immune regulator associated with the bladder repair program is a distinct subclass of dendritic cells (DCs), which moves into the subepithelial region of the bladder soon after the loss of the superficial epithelium. Here, we propose to determine the specific role of this DC subclass in epithelial repair. We will also examine the underlying basis for the Th2 bias of T cells recruited into the bladder following bouts of infection. Finally, we will investigate the possibility of reprograming Th2 primed bladder response into a Th1 type response by immunizing naïve and chronically infected mice with a vaccine antigen co-administered with Th1 biasing adjuvant. We suspect that such vaccines will not only protect bladder from future infection but also permit recovery of bladder function in these mice