Urinary-tract infections are the second most common bacterial infection in humans, and many of them are recurrent. A study published by Cell Press on February 14th in the journal Immunity reveals the cellular and molecular basis of recurrent bladder infections and suggests possible treatment strategies, such as vaccines, to prevent this common problem.
“Our study shows for the first time that the bladder is unable to mount an effective immune response to bacteria, which could explain the high frequency of recurrent infections,” says senior study author Soman Abraham of Duke University Medical Center. “These observations give us a new understanding of how immune responses are regulated in the bladder and may have implications for the treatment of recurrent infections.”
Urinary-tract infections are caused by Escherichia coli (E. coli), and the bladder in particular is prone to recurrent infections, but it is not known why. Some organs, such as the gut, that store waste products are considered “immune-privileged sites,” which need to tolerate the presence of microbes. As a result, the immune system does not activate as readily. Similarly, the bladder might require subdued immune responses to tolerate its contents (e.g., proteins in urine), prevent autoimmunity, and minimize tissue damage. If the bladder were an immune-privileged site, it might explain why it is prone to recurrent infections. But until now, the bladder has not been considered an immune-privileged site, so it has not been clear how this organ balances host defense with microbe tolerance.
In the new study, Abraham and his team found that E. coli persists in the bladders of mice for weeks after initial infection. These mice failed to produce antibodies against E. coli in response to initial infection or recurrent infection, suggesting that immune memory was impaired. The persistence of bacteria and suppressed immune responses in the bladder were mediated by the production of the molecule interleukin-10 by mast cells, which previously were known for their role in mounting immune responses against bacteria during the early stages of bladder infection. The results reveal that mast cells play a complex and key role in balancing host defense and tolerance in the bladder and in maintaining this organ as an immune-privileged site.
“The study suggests that provoking a strong immune response in the bladder through vaccination may be a possible strategy to prevent recurrent infections,” Abraham says. “Moreover, the findings could influence our understanding of additional conditions involving the bladder, such as bladder cancers.”
Bacterial Bladder Infections
Women are more susceptible to bladder infections and recurring bladder infections due to their anatomy. According to the National Kidney and Urological Diseases Information Clearinghouse, women who have already suffered two bladder infections are 80 percent more likely to have another one. Most bladder infections are caused by the bacteria strain Escherichia coli, more commonly known as E. coli, present in human’s intestines. E. coli bacteria are unusually resistant to antibiotics when they are present in the bladder, because they are able to hide within cells that are found inside the interior of the bladder and so are neither swept away with urination, nor easily treated with antibiotics.
A course of antibiotics provides temporary relief, but women who suffer recurring infections know that even a few days after stopping the antibiotics, they may already start to feel a burning sensation when urinating. Some women have a genetic vulnerability that allows the E. coli bacteria to lodge in their bladders. A urine culture will confirm whether E. coli is the cause of the infections and which antibiotic will be most effective in eliminating these bacteria. Some strains are resistant to certain antibiotics, which can also be revealed with a urine culture. Once the doctor knows which antibiotics will successfully combat the strain of E. coli present, she will prescribe an antibiotic to take for a few days every time symptoms present themselves or a small dosage before intercourse.
Recurrent cystitis, which is the medical term for repeated bladder infections, is not that uncommon, but for it to continue non-stop for 15 years is unusual and requires further investigation.
It is best to have mid-stream specimens of urine taken each time you have an infection, to identify the bacteria responsible. This makes sure you are having the right antibiotic, and can sometimes give a clue to an underlying cause.
It may well be that your doctor has already done this, and that you are taking ciprofloxacin because that is the only one that will work against the bacteria you have. But why is it there?
Sometimes it is a question of your anatomy, which allows bacteria into the bladder easily.
You may have heard of the expression ‘honeymoon cystitis’, where newlyweds, or women having frequent sexual intercourse for the first time, keep getting bladder infections.
This is because intercourse has the mechanical effect of massaging bacteria up the tube that connects the bladder to the outside (the urethra) because it runs up alongside the front wall of the vagina.
This problem usually settles, but in some women persists, and they get a bladder infection a couple of days after intercourse every time.
Immunity, Chan et al.: “Mast Cell IL-10 Drives Localized Immune Tolerance in Chronic Bladder Infection.”
Mary Beth O’Leary