Newly discovered ‘danger signal’ could boost vaccine development and allergy treatment

A study of how injured mouse cells trigger immune responses suggests new strategies to prevent and treat everything from parasites to allergies in humans.

The researchers hypothesized that intestinal cells damaged by parasitic worms call on the immune system by releasing adenosine triphosphate (ATP), which is metabolized into the adenosine nucleotide. Adenosine, in turn, binds to specific receptors on the surface of intestinal epithelial cells to trigger an immune response.

Members of the research team – who come mainly from Rutgers and Columbia, but also include researchers from Harvard, the University of Texas-Houston and the University of Ferrara – tested their theory by injecting worms to mice engineered to lack adenosine receptors on their epithelial cells. Unlike regular mice, which mount a robust immune response to these parasites, the specially engineered mice developed a markedly reduced immune response.

Parasitic worms known as helminths infect around 1.5 billion people, according to the study. A vaccine is not available, but this discovery of how the body naturally defends itself against helminths opens a path for development.

“If you combined a protein 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,” said lead author William Gause, director of Rutgers Institute for Infectious and Inflammatory Diseases (i3D), which is at Rutgers New Jersey Medical School. When the actual infection occurred, the memory immune response would be faster and stronger.”

“On the other hand, this finding suggests that it may be possible to treat allergies, which are essentially unwanted immune responses, with drugs that block adenosine receptors and reduce the immune response and harmful inflammation. partner,” Gause said.

So-called danger signals given off by injured cells are one of the two main ways the immune system learns about attackers. These signals are less well understood than other immune system triggers, molecules released by pathogens that are recognized by specific receptors on immune cells.

Gause said the release of ATP could turn out to be a common and important danger signal for injured cells. Every cell in the body contains ATP which can be released when injured.

The researchers are planning a follow-up study that will explore whether lung cells use the same signal to alert the immune system to invaders.

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Material provided by Rutgers University. Original written by Andrew Smith. Note: Content may be edited for style and length.

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