Recurrent urinary tract infection (rUTI) is a serious clinical problem, yet effective therapeutic options are limited, especially against multidrug-resistant uropathogens. In this review, we explore the development of a clinically relevant model of rUTI in previously infected mice and review recent developments in bladder innate immunity that may affect susceptibility to rUTI.
Chronic bladder inflammation during prolonged bacterial cystitis in mice causes bladder mucosal remodelling that sensitizes the host to rUTI. Although constitutive defenses help prevent bacterial colonization of the urinary bladder, once infection occurs, induced cytokine and myeloid cell responses predominate and the balance of immune cell defense and bladder immunopathology is critical for determining disease outcome, in both naïve and experienced mice. In particular, the maintenance of the epithelial barrier appears to be essential for preventing severe infection.
The innate immune response plays a key role in determining susceptibility to rUTI. Future studies should be directed towards understanding how the innate immune response changes as a result of bladder mucosal remodelling in previously infected mice, and validating these findings in human clinical specimens. New therapeutics targeting the immune response should selectively target the induced innate responses that cause bladder immunopathology, while leaving protective defenses intact.
aDepartment of Molecular Microbiology and Center for Women's Infectious Disease Research
bDepartment of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri
cDepartment of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
Correspondence to Scott J. Hultgren, Department of Molecular Microbiology, Washington University School of Medicine, Campus Box 8230, 660 South Euclid Avenue, Saint Louis, MO 63110, USA. Tel: +1 314 362 7059; e-mail: firstname.lastname@example.org