Posterior part of Drosophila larva with immune cells labelled in green. Image credit: Pavla Nedbalova (CC BY 4.0).
When confronted with an infection, immune cells are rapidly activated to fight the threat. However, like all cells, they require energy to act. While most cells reduce their activity when nutrients are scarce, the immune system cannot afford to do so, as halting its response could put the entire body at risk from infection.
It is not clear how immune cells manage this complex nutritional budgeting. Previous studies of fruit fly larvae infected with a parasitoid wasp revealed that immune cells secure extra energy by releasing a molecule called adenosine. This slows the metabolism of non-immune tissues, leaving more nutrients available for immune cells. However, the exact mechanism that immune cells use to produce adenosine remained uncertain.
To further examine this process, Nedbalova et al. – who are part of the research group that carried out the previous work – extracted activated immune cells from a parasitoid-infected larva and fed them a labelled amino acid. Tracing this label revealed an increase in the number of chemical units known as methyl groups that had been added to molecules within the cell. This process, known as methylation, can regulate metabolic activity within cells and produces adenosine as a byproduct.
Further genetic studies showed that if nutrient supplies were sufficient, the immune cells recycled this adenosine back into ATP, the body’s main energy currency. This suggests that if there were not enough nutrients to do this, the excess adenosine would slow the metabolism of non-immune cells, therefore securing more nutrients for the immune cells. Therefore, Nedbalova et al. hypothesise that these two processes could form the basis of a feedback mechanism that allows the immune cells to regulate their energy demands.
Taken together, the findings suggest that adenosine may act as a sensor to reflect immune activity, with it being released when the cells are stimulated and recycled if they have enough energy. This hypothesis still requires further testing but, as adenosine pathways are present across all organisms, it could have implications for many physiological and disease-related processes.
