Investigating macrophage-nerve crosstalk in homeostasis and post-stroke spontaneous urinary tract infection

ongoing

UTI is one of the most common bacterial infections, affecting >150 million individuals annually, worldwide. Unexpectedly, UTI is also the most common complication after stroke, occurring in up to 40% of patients. This suggests a dysregulation between the bladder and the brain, however this has never been studied. In other mucosal organs, neurons are in direct contact with tissue-resident macrophages and modulate their function during infection. Indeed, stroke causes striking changes to the immune compartment, including macrophages, in peripheral organs. As a result, stroke patients experience increased susceptibility to infection, alongside systemic inflammation, which is associated with neurological decline. In this project, I will investigate bladder macrophages in homeostasis and during acute stroke recovery. I will assess the impact of stroke on bladder immune cell-nerve crosstalk, including bladder macrophages and susceptibility to UTI. Specifically, I hypothesize that changes in macrophage-nerve crosstalk after stroke alters macrophage response to infection, leading to systemic inflammation and subsequent neurological decline. In collaboration with The University of Edinburgh, I will use a model of ischemic stroke in the lab of Dr Laura McCulloch to test this hypothesis. During this project, I will use state-of-the-art technologies such as spatial transcriptomics, 3D-imaging and spectral flow cytometry. Training at the University of Edinburgh, alongside in the host lab, will provide me with a unique set of skills combining the disciplines of immunology, microbiology and neurobiology. The expertise I will acquire in this project are in line with my career goals to become an independent researcher, and provide me with the tools to address a novel question in a largely unstudied area with clinical importance.