Cellular communication is essential for effective coordination of biological processes. One major form of intercellular communication occurs via the release of extracellular vesicles (EVs). These vesicles mediate intercellular communication through the transfer of their cargo and are actively explored for their role in various diseases and their potential therapeutic and diagnostic applications. Conversely, lipid droplets (LDs) are vesicles that transfer cargo within cells. Lipid droplets play roles in various diseases and evidence for their ability to transfer cargo between cells is emerging. To date, there has been little interdisciplinary research looking at the similarities and interactions between these two classes of small lipid vesicles. This review will compare the commonalities and differences between EVs and LDs including their biogenesis and secretion, isolation and characterisation methodologies, composition, and general heterogeneity and discuss challenges and opportunities in both fields.

Lipid droplets (LDs) are upregulated by host cells in the face of pathogen infection, however, the reason for this phenomenon remains largely unknown. Here, we demonstrate that virally induced LDs house a distinct and dynamic proteome containing key antiviral signalling pathway members, including the essential pattern recognition receptor; RIG-I, key adaptor proteins; STAT1 and STAT2 and prominent interferon inducible proteins; viperin and MX1. Changes in the LD proteome were underpinned by specific key changes in the lipidome of virally driven LDs, particularity in the phospholipid membrane. Following virus infection, key antiviral proteins formed complex protein-protein interactions on the LD surface, positioning this organelle as a key antiviral signalling platform for the first time. It is clear that dynamic regulation of both the proteome and the lipidome of LDs occurs rapidly following viral infection towards the initiation of a successful innate immune response.

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