Neutrophils in the lung (white circles) that engulf bacterial vesicles containing ATP (orange). Image Credit: Daniel Spari and Nadia Ennaciri (CC BY 4.0)
Sepsis is a severe condition often caused by the body’s immune system overreacting to bacterial infections. This can lead to excessive inflammation which damages organs and requires urgent medical care. With sepsis claiming millions of lives each year, new and improved ways to treat this condition are urgently needed. One potential strategy for treating sepsis is to target the underlying mechanisms controlling inflammation.
Inflamed and dying cells release molecules called ATP (the energy carrier of all living cells), which strongly influence the immune system, including during sepsis. In the early stages of an infection, ATP acts as a danger signal warning the body that something is wrong. However, over time, it can worsen infections by disturbing the immune response.
Similar to human cells, bacteria release their own ATP, which can have different impacts depending on the type of bacteria and where they are located in the body. However, it is not well understood how bacterial ATP influences severe infections like sepsis.
To investigate this question, Spari et al analysed how ATP is released from Escherichia coli, a type of bacteria that causes severe infections. This revealed that the bacteria secrete ATP directly in to their environment and via small membrane-bound structures called vesicles.
Spari et al. then probed a mouse model of abdominal sepsis which had been infected with E. coli that release either normal or low levels of ATP. They found that the ATP released from E. coli impaired the mice’s survival and lowered the number of neutrophils (immune cells which are important for defending against bacteria) at the site of the infection. The ATP secreted via vesicles also altered the role of neutrophils but in more distant regions, and it is possible that these changes may be contributing to the severity of sepsis.
These findings provide a better understanding of how ATP released from bacteria impacts the immune system during sepsis. While further investigation is needed, these findings may offer new therapeutic targets for treating sepsis.
