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

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.  Our data show that the pro-inflammatory polarization of
Drosophila macrophages is coupled to the production of the insulin
antagonist ImpL2 through the activity of the transcription factor HIF1α.
ImpL2 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. We demonstrated that analogically to Drosophila,
mammalian immune-activated macrophages produce ImpL2 homolog IGFBP7 in a
HIF1α-dependent manner and that enhanced IGFBP7 production by these cells
induces mobilization of lipoproteins from hepatocytes. Hence, the
production of ImpL2/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.