Lipid droplets (LDs), long viewed as inert storage organelles, are now emerging as active defenders against intracellular pathogens. Upon pathogen sensing, sentinel immune cells form specialized LDs that recruit lipid and protein mediators of host defence.

Remarkably, our recent study of adipose tissue colonization by Trypanosoma brucei revealed that ATGL, the enzyme initiating LD hydrolysis, is a crucial host-protective factor. These findings suggest that adipocytes, like professional immune cells, can remodel LDs in response to extracellular pathogens. We hypothesize that parasite sensing triggers adipocyte LD remodelling, leading to the extracellular release of antiparasitic and immunostimulatory factors. Leveraging the complementary expertise of the Figueiredo (adipocyte–trypanosome models), Demangel (LD biology and immunology), and Mattei (ultrastructural EM) laboratories, we will (i) define LD-derived protein and lipid mediators secreted by parasite-exposed adipocytes and their defensive functions, and (ii) resolve the proteomic and ultrastructural changes induced by infection signals in LDs. By integrating diverse cellular and molecular technologies, DELIGHT will establish causal links between LD remodelling, mediator release, and parasite control. This interdisciplinary project will redefine how adipocytes contribute to host defence and uncover a broader role for LDs in immunity against extracellular pathogens.

Simone Mattei (EMBL Heidelberg), Caroline Demangel (Institut Pasteur), Luisa Figueiredo (GIMM)