The bladder mucosa is in contact with the outside environment, which can expose it to a variety of pathogens, including uropathogenic Escherichia coli (UPEC). The result of pathogen colonization is urinary tract infection, which impacts 50% of women and 5% of men in the course of their lifetimes. Half of all those infected will experience recurrence within 6 months of the first UTI. In addition to adults, UTI are very common in infants, children, and the elderly. Despite the prevalence of this infection, vaccination attempts have been unsuccessful so far, and current treatment, antibiotic therapy, fails to prevent recurrent UTI, possibly due to the establishment of pathogen reservoirs or potentially insufficient immune memory. In this new study published in Science Immunology, the Mucosal Inflammation and Immunity team led by Molly Ingersoll identified a population of tissue-resident memory T cells that are essential for immune memory against recurrent exposure to UPEC.
Matthieu Rousseau and colleagues developed a mouse model of repeated UPEC infection and measured bladder bacterial burden to monitor which conditions impact the development of immune memory after a first UTI. They showed that while B cells do not play a role in immune protection, T cells are required for an effective immune response, although a specific bias toward any TH subset is not apparent. Limiting antigen persistence by reducing the bacterial inoculum or with antibiotics abrogates immune memory but does not alter TH populations. Using adoptive transfer and depletion strategies, they found that the only immune cell subset that correlates with immune memory is bladder tissue-resident memory T cells, and memory T cell populations in circulation or adjacent lymph nodes are dispensable. This study identifies a key player in immune memory against recurrent UTI in the bladder, offering an attractive new target for the treatment of recurrent UTI.
Tissue-resident memory T cells mediate mucosal immunity to recurrent urinary tract infection, Science Immunology, 2023
Read the press release: Immune memory: the best defense against bladder infections