ATP Danger Signal Mechanism could Lead to New Vaccines and Allergy Therapies

A collaborative team of researchers from Harvard University, Columbia University and Rutgers University has unlocked the mechanism of the danger signal adenosine triphosphate (ATP). The discovery could go on to influence the way in which immunomodulators, such as vaccines and allergy medications, are formulated. The study was published this week in Science News.

The team began with a hypothesis that ATP works as a danger signal when the human gut is under attack from parasites such as helminth worms. When parasites attack the cells lining the intestine, ATP is released and metabolized. The metabolized ATP, now adenosine, goes on to bind to the damaged epithelial cells to initiate the danger signal and immune response.

Helminths are one of the most common parasites to affect humans globally. The trespassers often enter the human host through contaminated foods or beverages before making a home in the intestinal tract, absorbing nutrients as the host unknowingly progresses toward a state of malnutrition. 

Since helminths affect such a large population without a vaccine available, the organisms make for an ideal research subject. The study involved injecting helminth parasites into mice without adenosine receptors. Rather than the typical immune response that is triggered when ATP is released from the damaged immune cells, these genetically altered mice were not able to launch the danger signal and subsequent immune response. Through deductive reasoning, this shows a connection between ATP and the way in which the immune system works to defend against allergies.

William Gause, director of the Rutgers Institute for Infectious and Inflammatory Diseases (i3D) and senior author of the study, explained the potential of this finding.

"If you combined a protein that's unique to helminths with an agonist that could trigger the adenosine receptor, you might be able to create a vaccine that would sensitize the immune system," he said. “When actual infection occurred, the memory immune response would be faster and stronger."

Gause’s suggestion to hijack the strong immune response to formulate a vaccine against helminth parasitic infection could also translate to a treatment with a wider spectrum.

"On the other side, this finding suggests that it may be possible to treat allergies, which are basically unwanted immune responses, with medications that block adenosine receptors and reduce the immune response and associated harmful inflammation,” he posited.

The next step for the research team is to find out how many other systems make use of ATP’s downstream activities to initiate a strong immune response, beginning with lung cells. ATP is plentiful in the human body, as a key component of the energy required for everyday activities. If the team finds that ATP drives more than just energy, and can be studied for immune system properties, further treatment applications could rapidly emerge.