PEROXISOME-METABOLISM IN THE REGULATION OF IMD (TNF) PATHWAY

Abstract

Aberrant NF-κB signaling drives chronic inflammation. Using Drosophila melanogaster, I investigated the Immune Deficiency (IMD) pathway, analogous to mammalian TNF signaling, which activates NF-κB against Gram-negative bacteria. My research identified peroxisomes as novel regulators of this pathway. Peroxisome-derived diacylglycerol (DAG) promotes the formation of Imd amyloid-like structures in macrophages, a critical step for NF-κB activation. Immunofluorescence and qPCR revealed that amyloid formation strongly correlates with transcription of antimicrobial genes, whereas peroxisome-deficient cells failed to form amyloids and mounted poor immune responses. Overall, my Ph.D. research uncovers a conserved immuno-metabolic circuit in which peroxisomes control TNF-NF-κB activation, providing insights into host defence and potential therapies for TNF-mediated immune disorders in humans.