Lipidomic data of macrophages isolated from adult fruit flies (Drosophila melanogaster) 24 hours post-infection

<p>The immune response is an energy-demanding process that must be coordinated with systemic metabolic changes redirecting nutrients from stores to the immune system. Although this interplay is fundamental for the function of the immune system, the underlying mechanisms remain elusive. </p> <p>Our data show that the pro-inflammatory polarization of <em>Drosophila</em> macrophages is coupled to the production of the insulin antagonist <em>ImpL2</em> through the activity of the transcription factor HIF1α. <em>ImpL2</em> production, reflecting nutritional demands of activated macrophages, subsequently impairs insulin signaling in the fat body, thereby triggering FOXO-driven mobilization of lipoproteins. This metabolic adaptation is fundamental for the function of the immune system and an individual's resistance to infection.</p> <p>We demonstrated that analogically to <em>Drosophila</em>, mammalian immune-activated macrophages produce <em>ImpL2</em> homolog IGFBP7 in a HIF1α-dependent manner and that enhanced IGFBP7 production by these cells induces mobilization of lipoproteins from hepatocytes.</p> <p>Hence, the production of <em>ImpL2</em>/IGFBP7 by macrophages represents an evolutionarily conserved mechanism by which macrophages alleviate insulin signaling in the central metabolic organ to secure nutrients necessary for their function upon bacterial infection.</p>