They discover an interspecies signaling pathway that unlocks mysteries about immunity and parasite development


Research led by a team from the University of Maryland (United States) has identified the first interspecific signaling pathway between a parasitic arthropod and its host, in which molecules present in the blood of a host animal trigger immunity and the development of a parasite.

The study has shown that when ticks feed on the blood of mice infected with the Borrelia burgdorferi bacterium, which causes Lyme disease, a mouse immune system protein binds to receptors on the tick’s cell surface and it signals the organs to develop more quickly, producing an immune response long before the bacteria itself can begin to infect the tick.

The study, published in the journal Science, identifies a potential target for tick-fighting vaccines or therapies aimed at preventing the spread of infections such as Lyme disease. The findings also provide important new insights into the evolution of biomolecular interdependencies between species and highlight, for the first time, both the integration of immunity and animal development and the adaptability of an ancient cellular signaling system or pathway that all plant and animal cells use to sense their environment and respond to it.

“This adaptive flexibility of a conserved cell signaling pathway is surprising,” explains Utpal Pal, senior author of the study and a professor at the Virginia-Maryland College of Veterinary Medicine in College Park. “It is surprising that this pathway that is present in all “From sponges to humans, is so flexible that it can adapt to accept a ligand (a binding molecule) from another, distant species. This tool that everyone has is being used in ways we never imagined,” he adds.

The finding suggests that other cell signaling pathways may have been adapted to novel uses in other organisms and points to a new area of ​​immunology and molecular biology ripe for further exploration.

Pal and his colleagues made their discovery while investigating tick immunity, a little-understood area of ​​tick biology. In their initial study, which sought to understand how ticks recognize Borrelia bacteria, the researchers fed ticks blood from Borrelia-infected or uninfected mice. By comparing the two groups, they found that the infected blood activated in the ticks a protein that normally produces energy inside cells. The protein is associated with a simple signaling pathway called JAK/STAT, present in all multicellular organisms.

As in all cell signaling pathways, a specific molecule senses something in the environment and binds to a receptor on the outside of the cell wall. This triggers a cascade of reactions inside the cell that activates or deactivates a specific gene and produces a response to the external stimulus detected.

Assuming that JAK/STAT was activated by Borrelia in the blood of the infected mouse, the researchers isolated the bacterium and injected it directly into ticks to see which molecules would bind to the JAK/STAT receptor. Surprisingly, the bacteria did not activate JAK/STAT. To find out what did it, the researchers removed Borrelia bacteria from the blood of infected mice and fed the “clean” blood to the ticks.

The JAK/STAT pathway kicked in, and the researchers discovered that a protein in the digestive system of ticks acted as the JAK/STAT receptor and had evolved to bind to the cytokine protein interferon, produced by the immune system of mammals infected with a tick. bacteria such as Borrelia.

The researchers also discovered that the JAK/STAT receptor and the JAK/STAT pathway are important for normal tick development, even though the pathway is not activated by an infected blood meal. When Pal and his colleagues knocked out the expressed gene that produces the JAK/STAT receptor, the ticks developed deformed legs, mouthparts, and digestive systems, and were unable to feed and complete the developmental cycle for further growth.

These results suggest that, in ticks, the JAK/STAT signaling pathway and receptor protein have evolved to integrate immunity with development. The bacteria compete with ticks for nutrients in the blood of an infected host, so when a tick receives the signal that its food is infected, it grows rapidly to use those nutrients before the bacteria can obtain them. Laboratory experiments agree that ticks fed Borrelia-infected mouse blood developed much faster than those fed uninfected mouse blood.

“Understanding that this pathway integrates immunity and development has important implications for potential tick-borne disease transmission prevention strategies,” says Pal, “because if the pathway is suppressed, ticks with malformed mouthparts cannot feed or transmit But what I also find really exciting is that we see this sort of early warning system, where the tick’s immune system indirectly detects a pathogen by using an immune response from its host rather than the pathogen itself, accelerating its own development,” he concludes.

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