Immunity to urinary tract infection: What the clinician should know

<h2>Abstract</h2><h3>Background</h3> Urinary tract infections (UTI), and especially recurrent UTI (rUTI), are among the most common indications for antibiotic treatment driving antimicrobial resistance. Recurrence is a defining feature of UTI, yet effective non-antibiotic strategies remain difficult to establish due to a knowledge gap in pathogenesis and influence of host immune responses and microbial communities. <h3>Objectives</h3> In this communication, we discuss mechanisms involved in immunity to UTI, the influence of host microbiomes on infection, and their clinical relevance for treatment and prevention strategies. <h3>Sources</h3> A literature review was conducted in PubMed using terms: innate immunity and UTI, adaptive immunity and UTI, urinary, vaginal, and gut microbiome and UTI, clinical management and UTI. <h3>Content</h3> Mucosal tissues, including the bladder, are protected by immune cells, though the composition of the immune compartment in healthy human bladders is less well-characterized compared to mice. Early inflammation supports UTI resolution, but sex differences in immune responses and factors, such as steroid hormone levels, may influence infection outcomes. Immune memory is less well understood and may be mediated by different mechanisms depending on the patient population. The urinary tract is not sterile and has its own microbiome. The bladder microbiome, potentially in communication with the gut and vaginal microbiomes, may influence the risk of UTI, through harboring uropathogens or more generalized dysbiotic interactions. <h3>Implications</h3> Conducting clinical trials addressing sex, age, immune responses, and the microbiome will lead to better understanding of UTI pathogenesis, host response, and risk of recurrence. Identification of immune or microbiome targets that can be modulated to decrease the risk of rUTI will contribute to the development of non-antibiotic alternatives, such as targeted vaccines, immunomodulatory approaches, or microbiota manipulation. These will, in turn, support improved UTI patient management.