Drosophila legs, with the muscles cells in green, and the immune cells in magenta. Image credit: Kierdorf et al. (CC BY 4.0)
The immune system helps animals fend off infections, but it also has a role in controlling the body’s metabolism – that is, the chemical reactions that sustain life. For instance, in fruit flies, high-fat diets can trigger the immune system, which results in cells becoming resistant to the hormone insulin and not being able to process sugar properly; this in turn leads to problems in sugar levels and shorter lifespans. This mechanism involves the release of an immune signal called unpaired-3 (upd3), which then binds to a receptor known as dome. Yet, it was unclear how exactly the immune system and metabolism work together, and whether their interactions are also important in flies on a normal diet.
To investigate, Kierdorf et al. stopped the activity of the dome receptor in the muscles of healthy flies. This led to an increase in the activity of the enzyme AKT, a protein critical to relay insulin-type signals inside the cell. As a result, insulin signaling was hyperactivated in the tissue, leading to decreased muscle function, unhealthy changes in how energy was stored and spent, and ultimately, a shorter life for the insects. Further experiments also identified blood cells called plasmatocytes (the flies’ equivalent of certain human immune cells) as a key source of the upd signal.
The findings by Kierdorf et al. shed a light on the fact that, even in healthy animals, complex interactions are required between the immune system and the metabolism. Further investigations will reveal if other body parts besides muscles rely on similar connections.
