The clinical implications of bacterial pathogenesis and mucosal immunity in chronic urinary tract infection

Urinary tract infections (UTIs) exert a significant health and economic cost globally. Approximately one in four people with a previous history of UTI continue to develop recurrent or chronic infections. Research on UTI has primarily concentrated on pathogen behavior, with the focus gradually shifting to encompass the host immune response. However, these are centered on mouse models of Escherichia coli infection, which may not fully recapitulate the infective etiology and immune responses seen in humans. The emerging field of the urobiome also inadvertently confounds the discrimination of true UTI-causing pathogens from commensals. This review aims to present a novel perspective on chronic UTI by linking microbiology with immunology, which is commonly divergent in this field of research. It also describes the challenges in understanding chronic UTI pathogenesis and the human bladder immune response, largely conjectured from murine studies. Lastly, it outlines the shortcomings of current diagnostic methods in identifying individuals with chronic UTI and consequently treating them, potentially aggravating their disease due to mismanagement of prior episodes. This discourse highlights the need to consider these knowledge gaps and encourages more relevant studies of UTIs in humans.