Though discovered almost a century ago, Adenosine Triphosphate, or more simply known as ATP, is one of the most interesting yet not clearly understood elements in biology. Popularly called "molecular unit of currency" ATP is the primary transporter of energy for all living cells. Outside of cells however, several reports demonstrated that extracellular ATP plays important roles in the immune system. During an infection, one of the first forms of defense employed by the innate immune response is a group of pattern recognition receptors that are programming to recognize the molecular patterns of invading pathogens. One such group of receptors, the NLRP family, are important components of inflammasomes that activate the inflammatory process.
Though previous studies have demonstrated how Adenosine-5'-triphosphate can activate the NLRP3 inflammasome, the exact physiological effects of extracellular ATP on NLRP3 inflammasome activation had never been investigated. Yang Xiang and Xuan Wang of the Key Laboratory of Animal Models and Human Disease Mechanism, Kunming Institute of Zoology, Chinese Academy of Sciences (KIZ, CAS) made an interesting discovery—ATP is released during bacterial infection. Developing a peritonitis model in mice, they found that ATP promotes the fight against bacterial infection, demonstrating a potential protective role played by ATP during bacterial infection that was related to NLRP3 inflammasome activation. These findings suggest a previously unproven role for ATP in initiating the immune response in organisms suffering infections.
Using their animal model, Xiang and Wang showed that the injection of ATP 4 hours before infection indeed reduced the mortality in mice with peritonitis. For the first time, a study directly demonstrated that the elevation of extracellular ATP actually may benefit the host defense against bacterial infection in vivo. Further testing revealed that the NLRP3 inflammasome exerted an important role in the ATP-mediated facilitation of the host fight against pathogens. As a danger signal, ATP is prevalent within the body and may be quite important in initiating the immune response when the host is suffering infection.
Though further research is needed to more deeply comprehend the detailed role and mechanism by which ATP protects hosts against microbial infections, Xiang and Wang’s work is an exciting first step in demonstrated a protective role for ATP in fighting infection. Given that the rise of a variety of drug-resistant infections that are unaffected by currently used antibiotics, searching for new alternatives in preventing infection will likely become an increasingly important venture.
The study “Adenosine-5'-Triphosphate (ATP) Protects Mice against Bacterial Infection by Activation of the NLRP3 Inflammasome” was recently published in PLoS One, and is accessible at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0063759.
(By Andrew Willden)
