Changes in lipid composition of host-derived extracellular vesicles following Salmonella infection

Abstract

ABSTRACT Extracellular vesicles are small membrane-bound structures secreted by host cells that are involved in a variety of functions and the transmission of cargo. Vesicular cargo contains a variety of biomolecules, including lipids. Limited research has focused on the cargo content of extracellular vesicles during infections, particularly the alterations in lipid cargo that occur following bacterial infections. Our study investigates the lipid composition of extracellular vesicles generated by RAW 264.7 macrophages before and after infection with Salmonella enterica serovar Typhimurium at 24 and 48 hours post-infection. Our results reveal that both time and infection conditions significantly alter specific lipids in host-derived small extracellular vesicles. The altered lipids primarily comprise glycerophospholipids, sphingolipids, and prenol lipids. Our findings have important implications for understanding molecular mechanisms underlying the trafficking of lipids to extracellular compartments during infection. IMPORTANCE This study delves into the previously unexplored territory of extracellular vesicle (EV) cargo and composition, specifically focusing on lipid composition changes in EVs following Salmonella infection. EVs play crucial roles in intercellular communication, carrying a variety of biomolecules. Investigating how these EV cargo lipids change post-infection with Salmonella is significant for understanding the molecular mechanisms underlying lipid trafficking during infection. Given the impact of lipid composition on EV function, this research uncovers distinct differences in the lipid profiles of EVs at different time points post-infection and between infected and uninfected macrophages. This study identified lipids that are differentially abundant in EVs produced by the host during infection, offering novel insights into the dynamics of lipid profiles in EVs during cellular processes and infections. This work advances our understanding of host-pathogen interactions, specifically lipid-mediated EV functions during infection.