The Drosophila PDGF/VEGF signaling pathway regulates host immunometabolism in response to parasitoid infection

Abstract

Mounting an immune response requires energy, but how that energy is reallocated at the organismal level remains poorly understood. In Drosophila melanogaster, infection by a parasitoid wasp triggers a systemic metabolic switch known as immunometabolism which is characterized by a shift in metabolic activity and the redistribution of resources away from organismal development and toward the production of a cellular immune response. We identify the PDGF/VEGF (PVF) signaling pathway as a key initiator of this immunometabolic switch. Genetic manipulation of PVF signaling alters infection outcomes, modulates systemic metabolite profiles, and reveals a direct trade-off between immune function and development. Our findings establish the Drosophila-parasitoid wasp system as a genetically tractable model for understanding the molecular basis of immunometabolism.