Bladder-draining lymph nodes support germinal centre B cell responses during urinary tract infection in mice

Abstract

Bacterial urinary tract infections (UTIs) are both common and exhibit high recurrence rates in women. UTI healthcare costs are increasing due to the rise of multi-drug resistant (MDR) bacteria, necessitating alternative approaches for infection control. Here, we investigated whether host adaptive immune responses can influence infection outcomes. We employed a mouse model in which wild-type C57BL/6J mice were transurethrally inoculated with an MDR UTI strain of uropathogenicEscherichia coli(UPEC). Firstly, we noted thatrag1-/-C57BL/6J mice harboured larger bacterial burdens than wild-type counterparts, consistent with a role for T and/or B cells in optimal control of UTI. Consistent with this, UTI triggered in the bladders of wild-type mice early increases of myeloid cells, including CD11chiconventional dendritic cells, suggesting possible involvement of these professional antigen-presenting cells. Importantly, germinal centre (GC) B cell responses developed by 4 weeks post-infection in bladder-draining lymph nodes of wild-type mice, and although modest in magnitude and transient in nature, could not be boosted with a second UTI. Thus, our data reveal for the first time in a mouse model, that Gram-negative bacterial UTI induces local B cell immune responses in bladder-draining lymph nodes, which could potentially serve to control infection.