Successful defense against pathogens is critical for survival. Microbes have developed many ways to invade larger organisms which in turn have evolved numerous immunity mechanisms. Lipid droplets (LDs) are dynamic and complex organelles that provide all eukaryotic cells with lipidic substrates for energy metabolism, membrane synthesis, and production of lipid-derived molecules. Probably for this reason, LDs are part of the infection cycle of viral, fungal, and bacterial pathogens. Mechanistic details of LD/pathogen interactions are largely unknown, but many pathogens stimulate LD biogenesis. The current view is that LDs are “hijacked” to provide lipids and energy to pathogens for effective and rapid growth.
Our recent work has challenged this dogma and demonstrated that LDs are organelles that actively participate in the Drosophila organismal antibacterial response. This new type of innate immunity could well be at work in every infected tissue of our body since all cells accumulate LDs. Preliminary data, specially generated for this project, supports the idea that this innate immune system has been conserved during evolution.
Thus, based on solid preliminary data, we here propose a multidisciplinary research project to characterize cells, sites, and mechanisms of action of this innate immunity. Whole animal studies will determine cells of interaction, high-resolution ultra-structural analysis of infected tissues and cellular models will determine sub-cellular locations and details, single-organelle biophysical studies and in vitro LD-bacteria killing assays combined with ultra-structural studies will develop a mechanistic understanding of the process, and comparative proteomics will identify protein complexes conferring chemotaxis and antibiotic activity to LDs.
In conclusion, here we present a project designed to identify and characterize a new innate immune system that will be paradigm-shifting in Immunology, Physiology, and Cell Biology. Further, the combination of the detailed single-organelle killing assays with the super-resolution studies specially developed for these studies will allow unprecedented mechanistic details establishing an entirely new dimension in the ongoing host pathogen conflict.