Innate immune signaling in Drosophila shifts anabolic lipid metabolism from triglyceride storage to phospholipid synthesis to support immune function

• DOI: 10.1371/journal.pgen.1009192
• Publication Date: 2020-11-23T19:43:27Z
• Authors: Brittany A. Martínez; Rosalie G. Hoyle; Scott Yeudall; Mitchell E. Granade; Thurl E. Harris; J. David Castle; Norbert Leitinger; Michelle L. Bland
• Keywords: Lipid droplet

During infection, cellular resources are allocated toward the metabolically-demanding processes of synthesizing and secreting effector proteins that neutralize kill invading pathogens. In Drosophila , these effectors antimicrobial peptides (AMPs) produced in fat body, an organ also serves as a major lipid storage depot. Here we asked how activation Toll signaling larval body perturbs homeostasis to understand cells meet metabolic demands immune response. We find genetic or physiological leads tissue-autonomous reduction triglyceride is paralleled by decreased transcript levels DGAT homolog midway which carries out final step synthesis. contrast, Kennedy pathway enzymes synthesize membrane phospholipids induced. Mass spectrometry analysis revealed elevated phosphatidylcholine phosphatidylethanolamine species bodies with active signaling. The ER stress mediator Xbp1 contributed Toll-dependent induction enzymes, was blunted deleting AMP genes, thereby reducing secretory demand elicited activation. Consistent induction, volume expanded signaling, determined transmission electron microscopy. A functional consequence reduced impaired response bacterial infection. Our results establish induces shift anabolic metabolism favor phospholipid synthesis expansion may serve immediate for secretion but long-term insufficient nutrient storage.