A serine-folate metabolic unit controls resistance and tolerance of infection

Immune activation drives metabolic change in most animals. Immune-induced metabolic change is most conspicuous as a driver of pathology in serious or prolonged infection, but it is normally expected to be important to support immune function and recovery. Many of the signalling mechanisms linking immune detection with metabolic regulation, and their specific consequences, are unknown. Here, we show thatDrosophila melanogasterrespond to many bacterial infections by altering expression of genes of the folate cycle and associated enzymes of amino acid metabolism. The net result of these changes is increased flow of carbon from glycolysis into serine and glycine synthesis and a shift of folate cycle activity from the cytosol into the mitochondrion. Immune-induced transcriptional induction ofastrayandNmdmc, the two most-induced of these enzymes, depends onDifandfoxo. Loss ofastrayorNmdmcresults in infection-specific immune defects. Our work thus shows a key mechanism that connects immune-induced changes in metabolic signalling with the serine-folate metabolic unit to result in changed immune function.