Targeting type 2 immunity in the battle against chronic urinary tract infection

The bladder is a unique and often forgotten mucosal site. When the bladder is exposed to bacterial pathogens it sheds superficial epithelial cells to eliminate the invading bacteria. The bladder epithelium has to rapidly repair itself to maintain epithelial integrity to prevent exposure to toxins in the urine. If this repair response is insufficient it may leave the host susceptible to infection. If the repair response is exaggerated it may lead to remodelling and fibrosis of the tissue. Type 2 immune cells, such as group 2 innate lymphoid cells (ILC2) are critical regulators of epithelial barrier function at other mucosal sites. But their function in the bladder are poorly understood. This project will use ILC2 deficient mice to study the functional role of these immune cells in homeostasis and in response to uropathogenic E. coli infection. We will also use reporter mice to detect when and where these immune cells are located in the bladder using 3-dimensional confocal imaging of optically transparent tissue and high parameter flow cytometry. RNA-seq will be used to identify the unique transcriptional profile of urinary tract ILC2. Finally we will explore the feasibility of repurposing emerging and established type 2 immunotherapies as a novel treatment strategy for persistent and recurrent urinary tract infections.