Nat E. Wu Jianxuan and others revealed the immunological causes of the high recurrence rate of urinary tract infections.

Urinary tract infections (UTI) is a general term for infections caused by various bacteria invading urinary system organs such as urethra, bladder and kidney.urinary tract infection is one of the most common bacterial infections, especially in women.it is estimated that approximately half of women worldwide will experience at least one urinary tract infection in their lifetime [1].the pathogenesis of urinary tract infection is that bacteria invade the bladder through urethra and proliferate and invade bladder epidermal cells.in order to resist the bacteria invading the epidermal cells, the immune response in the bladder can cause the exfoliation of the whole surface cells of the bladder epidermis [2].due to the structural reasons of urinary system, the infection is generally limited to the bladder, but in serious cases, bacteria will invade the kidney along the ureter, causing more serious inflammatory reaction [3].diagram 1 urinary tract structure and the common immune cells in each organ. 3. Urinary tract infection is not only incidence rate high, but also the probability of infection recurrence.in different studies, the recurrence rate was between 27% and 44%, which was much higher than the recurrence rate of bacterial infection in other parts of the human body [4].this phenomenon does not seem to conform to the basic immunological principles.generally, the host will establish an adaptive immune response against the pathogen after it is invaded.after that, if the same pathogen invades again, the host specific immune response will start quickly and kill the pathogen quickly.strong specific immunity can even prevent the same pathogen from re infection.but in fact, if someone has had a urinary tract infection, the probability of her (his) re infection is not reduced, but greatly increased [5].for a long time, no one has been able to give an immunological explanation for the high recurrence rate of urinary tract infection.the possible reason is that it is difficult to isolate and culture immune cells (such as Th cells) that produce specific responses in mouse bladder models used to study urinary tract infection.on May 18, 2020, the soman Abraham research group of Duke University Medical Center published a highly polarized Th2 bladder response to infection promoters epithelial repair at the expense of preventing new infections, which provides a possible immunological explanation for the high recurrence rate of urinary tract infection.that is, the immune response in bladder focuses on the use of IL4 produced by Th2 cells in specific immune response to repair bladder epidermal cells damaged and exfoliated in bacterial infection, while Th1 cells producing IFNgamma in specific immune response are inhibited. therefore, the specific immune response cannot produce strong enough bactericidal capacity after infection [6]. in this study, the researchers found that bladder clearance of bacteria was enhanced in Th2 deficient IL4 - / - mice. therefore, the researchers hope to further isolate and analyze Th2 cells in bladder. in order to overcome the technical difficulties, the researchers used Th cell fluorescent reporter mice which were widely used in immunology research in recent years, which greatly improved the sensitivity of analyzing bladder cells. after careful study, the researchers found an unusually high percentage of Th2 cells in the bladder. classical immunological results show that the activation and differentiation of Th2 cells can inhibit the production of Th1 cells with obvious bactericidal effect [7]. this phenomenon was also observed in the bladder, i.e., the proportion of Th1 cells was low and did not increase significantly after multiple infections, corresponding to the high proportion of Th2 cells in the bladder. Th1 cells were significantly increased after Th2 cells were knocked out. Figure 2 Th cells in the bladder [6] the researchers speculate that if Th2 cells in the bladder have no bactericidal effect, and can inhibit Th1 cells with obvious bactericidal effect, Th2 cells should have more important role besides sterilization. classical immunological studies have shown that Th2 cells have a strong repair effect on tissue damage [8]. after infection of the bladder, a large number of surface epidermal cells fall off. If the bladder cannot be repaired quickly, the high salt and acid content in urine will seriously damage the bladder tissue. Therefore, the researchers speculate that the activation of Th2 cells is to repair the bladder epidermis. after a large number of experiments, researchers found that Th2 cells do play an important role in the repair of bladder epidermis. however, due to the strong repair reaction, the bladder epidermis was significantly thickened after repeated infection, and the tissue structure of the whole bladder changed greatly, which further affected the bladder function - the frequency of micturition in mice with multiple infections was greatly increased. further studies have shown that the highly activated Th2 cells are mediated by the unique cd301b + OX40L + dendritic cells (DC) in the bladder. to sum up, this study revealed a possible immunological reason for the high recurrence rate of urinary tract infection, that is, the abnormally strong Th2 cell response was activated by the unique cd301b + OX40L + dendritic cells in the bladder, leading to the inhibition of the bactericidal Th1 cells in the bladder. at the same time, the tissue structure and urination function of bladder were also affected after multiple bacterial infections due to the strong repair function mediated by Th2 cells. after multiple urinary tract infections, patients urinate more frequently, which has been observed in clinic. in the future, it will be helpful to design clinical therapy to reduce the recurrence rate of urinary tract infection if we can explore whether there is abnormally elevated Th2 response in patients with multiple recurrence of urinary tract infection. the first author of the study was Wu Jianxuan, a doctoral student in the Department of immunology at Duke University Medical Center, and the corresponding author was Dr. soman Abraham, distinguished professor of grace Kerby, Duke University Medical Center. 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