Urinary tract infections (UTIs) are the second most common bacterial infection with high recurrence rates (1). With the rise of multi-drug resistant (MDR) bacteria, UTI treatment is becoming increasingly difficult and costly. In 2020 alone, UTIs cost the Australian healthcare system $909 million (2), a figure which is estimated to increase unless we can combat antibiotic resistance. Here we investigated adaptive immune responses in a mouse model of MDR UTI, and whether they contribute to controlling infection, in the hopes of finding alternative therapies for UTI.
C57BL/6J wild-type mice were transurethrally inoculated with an MDR UTI strain of Gram-negative uropathogenic Escherichia coli (UPEC), depositing bacteria directly into the bladder. A group of mice were inoculated a second time after 1 week, to simulate administration of an adjuvant. Mice were then monitored for 4-7 weeks. Flow cytometry was used to characterise B cell populations in bladder-draining lymph nodes of wild-type mice. Bladders and urine were also collected at various time-points to assess bacterial numbers.
In bladder-draining lymph nodes of wild-type mice, germinal centre (GC) B cell responses had developed by 4 weeks post inoculation, and subsided by 7 weeks. Mice given a second inoculation did not have enhanced GC B cell responses, suggesting that successive inoculations in the bladder do not elicit stronger humoral immunity despite it being the primary site of infection. In conclusion, our data suggest for the first time in a mouse model, that Gram-negative bacterial UTI induces humoral immune responses in local lymph nodes, which could potentially help clear infection. Boosting this transient response could greatly aid current therapies in terms of bacterial clearance, and ideally reduce the high levels of recurrence in UTI.