Uropathogen and host responses in pyelonephritis

Urinary tract infections (UTIs) are among the most common bacterial infections seen in clinical practice. The ascent of UTI-causing pathogens to the kidneys results in pyelonephritis, which can trigger kidney injury, scarring and ultimately impair kidney function. Despite sizable efforts to understand how infections develop or are cleared in the bladder, our appreciation of the mechanisms by which infections develop, progress or are eradicated in the kidney is limited. The identification of virulence factors that are produced by uropathogenic Escherichia coli to promote pyelonephritis have begun to fill this knowledge gap, as have insights into the mechanisms by which kidney tubular epithelial cells oppose uropathogenic E. coli infection to prevent or eradicate UTIs. Emerging data also illustrate how specific cellular immune responses eradicate infection whereas other immune cell populations promote kidney injury. Insights into the mechanisms by which uropathogenic E. coli circumvent host immune defences or antibiotic therapy to cause pyelonephritis is paramount to the development of new prevention and treatment strategies to mitigate pyelonephritis and its associated complications. The bladder and kidney engage adaptive and innate immune responses to prevent urinary tract infections and minimize tissue injury following infection. Here, the authors describe the mechanisms used by uropathogenic bacteria to establish and promote kidney infection, as well as the immune defence mechanisms used by resident kidney cells and infiltrating immune cells to eradicate infection.