"The bladder is a unique mucosal barrier devoid of colonizing microbiota and organized lymphoid structures. This research project will examine bladder immunobiology, specifically as it relates to urinary tract infection (UTI) and bladder cancer. Notably, UTI is second only to respiratory infection in prevalence, and bladder cancer is the fifth leading cause of cancer. While commonalities between UTI and bladder cancer may not be immediately apparent, the most effective treatment for transitional cell carcinoma is intravesical instillation of BCG, or the direct introduction of bacteria into the bladder lumen. We will investigate bladder immune responses following uropathogenic E. coli (UPEC) or BCG instillation, with the aim to identify how dendritic cells (DCs) and T cells behave following bacterial interactions with what is a unique mucosal surface in the body. Specifically, we will test the hypotheses that (i) bladder-resident macrophages acquire UPEC antigen in the bladder and sequester it from DCs, limiting antigen presentation, while lymph node-resident DCs capture disseminated BCG and efficiently present it; and (ii) DCs that do capture UPEC antigen lack the ability to cross-present antigen whereas BCG-antigen loaded DCs have a greater capacity to activate CD8+ T cells. These hypotheses are based on animal model and clinical observations and will help establish a scientific foundation for exploring strategies to enhance UPEC antigen-specific responses, taking lessons from BCG’s capacity to induce cross-priming. The goal of these studies is to understand the differential outcomes in adaptive immune responses to BCG or UPEC thereby defining strategies to enhance clearance of UPEC and improve the efficacy of BCG-mediated tumor immunity. My dual training as a microbiologist and immunologist will ensure that attention is given to both the bacterium and the host in defining the differential regulation governing the respective disease processes."
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