Lipids that directly regulate innate immune signal transduction

Pattern Recognition Receptors (PRRs) detect evidence of infection and tissue damage. The activation of these receptors and their downstream signal transduction pathways initiate a protective immune response. These signaling pathways are influenced by their spatial context, and precise subcellular positioning of proteins and protein complexes in these pathways is essential for effective immune responses in vivo. This organization is not limited to transmembrane proteins that reside in specific organelles, but also to proteins that engage membrane lipid head groups for proper positioning. In this review, we focus on the role of cell membranes and protein–lipid interactions in innate immune signal transduction and how their mechanisms of localization regulate the immune response. We will discuss how lipids spatially regulate the sensing of damage or infection, mediate effector activity, and serve as messengers of cell death and tissue damage.