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

Waring-Sparks, A. L.; Kpirikai, A. Y.; Yang, J.; Baddireddi, R.; Marun, N.; Bretz, N. M.; Gosnell, H.; Malik, H.; Hendrix, D. A.; Mortimer, N. T.

2025-10-01 biochemistry
10.1101/2025.10.01.679819 bioRxiv
Show 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.

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