Sphingolipid-enriched membrane microdomains contribute to a variety of cellular processes, including signal transduction and vesicle trafficking. Interestingly, a number of pathogens exploit the endocytic properties of Sphingolipid-enriched membrane microdomains to enter into host cells. In particular, N. meningitidis modulates sphingolipid levels on brain endothelial cells and uses ceramide-rich membrane platforms as a port of entry into non-phagocytic cells.
Ceramides can further be metabolized to sphingosine-1-phosphate (S1P), a sphingolipid metabolite that has both cell-intrinsic and cell-extrinsic activity, affecting cell homeostasis and function. We will focus on the cell-extrinsic function of S1P, where it acts as a ligand for a family of five G-protein coupled receptors, known as S1P receptors (S1P1-5) and aim to characterize the role of S1P and S1P1-2 during the inflammatory response and the modulation of barrier permeability and integrity during the pathophysiology of meningococcal