![]() However, studies in mice reveal that even after the infection is resolved, an appreciable population of UPEC persists within BECs in a quiescent phase for extended periods of time 70. ![]() If untreated, UTIs tend to be self-limiting and naturally resolve within several days 71. Once UPEC become intracellular, they are protected from elimination by urine or the immune system, enabling them to initiate an acute infection. Uropathogens seem to achieve this feat by hijacking the innate capacity of BECs to regulate bladder volume. Arguably, the capacity to penetrate the highly impregnable bladder epithelial barrier and seek refuge in bladder epithelial cells (BECs) is a critical initiating step of infection in the urinary tract. Bacterial survival in the urinary tract is also promoted by their expression of cell surface capsules, which enable them to resist the bactericidal actions of complement and phagocytic cells 70. Uropathogens also secrete toxins, such as haemolysin and cytotoxic necrotizing factor, which disrupt the epithelial barrier and enable access to the underling tissue 68, and siderophores, which enable bacteria to chelate iron that is important for growth 69. Uropathogens express certain key virulence factors that enable them to successfully establish infection in the urinary tract these include adhesive fimbriae, which enable bacteria to adhere avidly to specific receptors on the urothelium, and flagella that enable bacteria to swim along the urinary tract including ‘upstream’ from the bladder to the kidneys 67. Most of these bacteria originate from the gut and reach the urinary tract by progressive colonization via the perineal region 3. More than 80% of urinary tract infections (UTIs) in healthy individuals are caused by uropathogenic Escherichia coli (UPEC), with the remainder being caused by other enteric Gram-negative bacteria and some Gram-positive bacteria 3. However, most of the time the urinary tract resists infection, and if infection is established, it remains contained within this tract unless predisposing conditions exist 4. Uropathogens express common virulence factors that enable them to successfully establish infection in the urinary tract ( BOX 1). The majority of urinary tract infections (UTIs) in healthy individuals are caused by uropathogenic Escherichia coli (UPEC) that originate from the gut 3. NK, natural killer TLR, Toll-like receptor. ![]() These cells are located underneath the basal epithelium and function as sentinels to sense infection and recruit neutrophils and LY6C + macrophages from the bladder. The major resident immune cells in the bladder include mast cells and LY6C − macrophages. The ureters, urethra and bladder constitute the lower urinary tract, and several layers of stratified epithelial cells that line the bladder function as the first line of defence. In addition, there is a large network of lymphatic vessels in these organs, which connects to the renal lymph nodes. ![]() Many of the immune-competent cells, including dendritic cells (DCs) and macrophages, are aggregated in the interstitium in close proximity to both the tubular epithelium and blood vessels. The upper urinary tract is comprised primarily of the kidneys, and the filtration function of the kidneys is performed by hundreds of thousands of nephrons, each of which is composed of a glomerulus and a double hairpin-shaped tubule. Organization of immune-competent cells along the urinary tractĪ variety of cell types are responsible for initiating immune responses along the urinary tract.
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