Extracellular adenosine modulates host-pathogen interactions through regulation of systemic metabolism during immune response in Drosophila.

What happens if we don't deliver enough energy to the immune system? Or vice versa, if we deliver it too much? How is the energy management of the body regulated during immune reactions? If the immune system does not have enough energy, it cannot be effective enough to fight the pathogen. This is quite logical. But what happens if there is more energy is released for immunity? The organism does not have unlimited supplies and so it has to be very careful with energy. It is also often speculated that the released energy is used not only by the immune system but also by the pathogen itself. How to ensure that the host does not unnecessarily feed pathogens? These are important evolutionary-ecological questions, but it is not easy to verify experimentally.

For experimental verification, it is necessary to have a good model system, preferably an easy to manipulate model organism with a well defined model of infection. Adam Bajgar and Tomáš Doležal from the Drosophila Molecular Integrative Physiology Laboratory have such a model system. Thanks to the genetic model of fruit flies, they are able to regulate the amount of energy released for the immune response and watch how it affects the host's fight with the pathogen. They found that if the immune system does not get enough energy, it is really inefficient and fruit fly will succumb to infection. However, increasing the amount of energy released can sometimes improve the immune response, but sometimes it can help pathogens at the expense of the host, depending on the type of infection. In addition, these experiments have shown that immune cells behave selfishly to usurp energy during the threat, but that they can also limit their selfishness. At the beginning of the reaction, immune cells release adenosine that attenuates energy consumption by other tissues, but later they release an enzyme that degrades adenosine and thus stops their selfishness.

Bajgar A, Dolezal T (2018) Extracellular adenosine modulates host-pathogen interactions through regulation of systemic metabolism during immune response in Drosophila. PLoS Pathog 14(4): e1007022.

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