Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense

TLDR

Lipid droplets accumulate in cells as lipid storage organelles and serve as a source of nutrients for many pathogens, positioning them as potential targets in host defense. The study seeks to inform future antimicrobial strategies in the age of antibiotic resistance. Proteins of innate immunity assemble on lipid droplets after LPS stimulation, causing the droplets to detach from mitochondria and shift cells from oxidative phosphorylation to aerobic glycolysis, thereby enabling the droplets to kill pathogens directly and create a metabolic environment that favors host defense. Bosch et al.; Science, this issue p.

Abstract

Cells drop a bomb on pathogens Lipid droplets (LDs) accumulate in cells to serve as lipid storage organelles. They are also an attractive source of nutrients for many pathogens. Bosch et al. show that various proteins involved in innate immunity form complexes on LDs in response to bacterial lipopolysaccharide (see the Perspective by Green). Upon activation, LDs became physically uncoupled from mitochondria, driving a shift in cells from oxidative phosphorylation to aerobic glycolysis. This work highlights the ability of LDs both to kill pathogens directly and to establish a metabolic environment conducive to host defense. This may inform future antimicrobial strategies in the age of antibiotic resistance. Science , this issue p. eaay8085 ; see also p. 294