Las urinary infections are one of the bacterial pathologies most common in human beingsbut they rarely evolve into serious complications, such as pyelonephritiswhich affects the kidneys.
And new study carried out by scientists from the Cambridge University in the United Kingdomwhich was published in the magazine Science Translational Medicine, revealed why many people have a natural protection.
As the scientists highlighted, they discovered the mechanisms behind this protection, by focusing on the role of components of the immune system what are they called neutrophil extracellular traps (NETs). These are DNA networks released by neutrophils that act as traps for pathogens.
Los Neutrophils are a type of white blood cell and they form the first line of defense of the immune system against the development of infections. You can use a absolute neutrophil count to determine if infection, inflammation, leukemia, or other conditions are present.
To fight infections, neutrophils employ several mechanisms, including a process known as NETosthrough which they expel their DNA in the form of networks (the NETs).
These traps contain antimicrobial proteins that not only trap, but also destroy pathogens such as bacteria and fungi. This process was first described in 2004 by the team Arturo Zychlinsky.
The new study led by Andrew Stewart y Menna Clatworthy, University of Cambridgefocused on the urinary tract, which is the system in the body that produces, stores, and eliminates urine.
They found that neutrophils undergo a specialized cell death that allows them partially disintegrateand release its genetic material and the antimicrobial proteins contained in its granules.
This cell death is not typical apoptosis (programmed cell death), but an active form that results in the creation of NETs, which are a sticky mesh.
These networks serve as a crucial antibacterial defense against infections, trapping bacteria that try to migrate to the kidneys from the lower urinary tract.
During the research, experiments were done on mouse and human models. On the one hand, scientists used rodents in which they induced urinary tract infections (UTI), by introducing the bacteria Escherichia coli (E. coli) in the bladder.
In these animals, they observed how NETs, formed by the release of DNA from neutrophils, interact with the uromodulina (UMOD) present in urine. This action forms networks that trap bacteria and prevent them from ascending from the bladder to the kidneys.
The mice were treated with an inhibitor of PADI4an enzyme essential for the formation of NETs. The results showed that inhibition of the neutrophil death process caused a increased severity of infectionsince the bacteria managed to ascend to the kidneys. In control rodents, where NET formation was not inhibited, the bacteria were captured before reaching the kidneys.
The researchers also studied the urine of healthy people and identified the networks NETs. Through imaging techniques and proteomic analysis, it was observed that they were made up of DNA and antimicrobial proteins.
These networks can trap bacteria, reinforcing the hypothesis that NETs are a fundamental part of the natural defense against ascending infections. Likewise, they recognized the limitations of the study. The use of animal models implies a limitation for the direct extrapolation of the results to human beings.
There is also difficulty in analyzing the kidney disorder, called pyelonephritis, due to its low incidence in the data of the UK Biobank. There were also ethical restrictions that prevent experimental studies in humans to fully validate the findings.
In dialogue with Infobaethe doctor Florencia Sabbioneresearcher in immunology at CONICET and the National Academy of Medicine of Argentinacommented on the study: “Scientists found networks formed of DNA in the urine of healthy people, which are released by the defense system to prevent bacteria from spreading. In this way, a bacterial infection would not reach the kidneys.”
It was also observed -said Sabbione- that “people with genetic deficiencies that prevent them from producing these networks are more susceptible to having bacterial infections in intensive care. The results could be useful to determine the greater or lesser risk of developing infections in intensive care.”
