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Macrophage-derived insulin antagonist ImpL2 induces lipoprotein mobilization upon bacterial infection

G. Krejčová, C. Morgantini, H. Zemanová, VM. Lauschke, J. Kovářová, J. Kubásek, P. Nedbalová, N. Kamps-Hughes, M. Moos, M. Aouadi, T. Doležal, A. Bajgar

. 2023 ; 42 (23) : e114086. [pub] 20231009

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc24000434

Grantová podpora
20-14030S The Czech Science Foundation (GACR)
23-06133S The Czech Science Foundation (GACR)
20-09103S The Czech Science Foundation (GACR)
050/2019/P USB Grant Agency

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.

Citace poskytuje Crossref.org

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