To borrow an analogy from my PI, Dr. Soman Abraham, imagine you are at your home relaxing. You had a long day at work so you sit back on your La-Z-Boy reclining sofa and sip a cool glass of water. Little unbeknownst to you, there is a hive of bees swarming in the vents of your sweet home forming an army that is preparing to attack you. Eventually, you notice a strange buzzing sound coming from your kitchen walls and call a bee exterminator to come to look at the situation. The exterminator finds the bees–but he unknowingly does not get rid of all the bees! The few bees that remain inside your house walls linger and repopulate in preparation to launch another attack.
That, my friends, is how urinary tract infections (UTI) reoccur.
The prevalence and recurrence of UTIs are much higher for women than men due to the rising numbers of the immuno-compromised and elderly. Uropathogenic Escherichia coli (UPEC), the pathogen that causes many UTIs, originates from our guts. The urinary tract has innate immune responses to expunge bacteria from the body. Epithelial cells that line the bladder wall are the primary defense against the pathogen. Not only are they responsible for protecting the underlying tissue from toxins in urine, but they also inhibit the growth of bacteria through the secretion of antibacterial agents. Other innate immune cells that have a key role in regulating UPEC include neutrophils, macrophages, and mast cells. Despite these mechanisms that are put in place, UPEC still finds a way to invade the bladder epithelial cells. Once they become intracellular, they become increasingly more difficult for the urinary immune cells to find and expunge them. Occasionally, some bacteria leave the haven that is the bladder epithelial cells and goes out into the bladder lumen. Once that happens, they repopulate to cause another infection. But even when the urinary immune cells get rid of them, the other bacteria that are hiding in the bladder wall unknown to the immune cells would occasionally leave the bladder wall to cause yet another infection, hence stimulating the recurrence of UTIs.
It has been believed that mast cells are responsible for sensing bacterial pathogens and then relaying that information to other cells, but micrographs of our bladder wall show that sensory neurons, which are responsible for “sensing things,” are situated right next to mast cells. This has researchers asking whether it is actually sensory neurons that are detecting the pathogen and then sending that signal to mast cells. This summer, I will be investigating whether sensory neurons in the bladder are activated upon bacterial challenge. To do this, I will process the bladder tissue of infected mice, section the tissue using a cryostat, and perform immunofluorescent staining on the tissue. The antibody β-Tubulin 3 will stain for all neurons, while p-ERK will stain for all activated neurons.
So far the work I’ve been doing in the lab is thrilling and I feel honored to be working on a project that will allow researchers to understand the way in which our bladder immune system reacts to pathogens in hopes of forming preventive methods to lessen the burden of recurring UTIs.
