Acute Dietary Restriction Acts via TOR, PP2A, and Myc Signaling to Boost Innate Immunity in Drosophila

Abstract

Dietary restriction promotes health and longevity across taxa through mechanisms that are largely unknown. Here, we show that acute yeast restriction significantly improves the ability of adult female Drosophila melanogaster to resist pathogenic bacterial infections through an immune pathway involving downregulation of target of rapamycin (TOR) signaling, which stabilizes the transcription factor Myc by increasing the steady-state level of its phosphorylated forms through decreased activity of protein phosphatase 2A. Upregulation of Myc through genetic and pharmacological means mimicked the effects of yeast restriction in fully fed flies, identifying Myc as a pro-immune molecule. Short-term dietary or pharmacological interventions that modulate TOR-PP2A-Myc signaling may provide an effective method to enhance immunity in vulnerable human populations.

Keywords: Myc; dietary restriction; innate immunity; melanization; pathogenic bacterial infection; phenoloxidase; protein phosphatase 2A; target of rapamycin; tolerance; yeast restriction.