Biophysical Society Thematic Meeting | Ascona, Switzerland

Liposomes, Exosomes, and Virosomes: From Modeling Complex Membrane Processes to Medical Diagnostics and Drug Delivery

Monday Speaker Abstracts

Liposomes Activate Innate Immunity Cascades Through Recognition of Toll-like Receptors Jean-Marie Ruysschaert. Université Libre de Bruxelles, Brussels, Brabant, Belgium. Toll-like receptors are major members of the Pattern Recognition Receptors (PRRs) from the innate immune system, which recognize bacterial or viral components (like lipopolysaccharides, flagellin, lipopeptides, single-stranded RNA) and transmit a signal to the cell that brings the immune system in a “state of emergency”, ready to react to a microbial invasion. Recently, apart their role in recognition of pathogen-associated patterns, we provided evidence that non-bacterial ligands like nanoliposomes do activate innate immunity cascades through recognition of Toll- like receptors. Using chimeric construction, molecular docking and site-directed mutagenesis we identified a new binding site which does not correspond to the known natural ligand binding site.This new concept that non-bacterial ligands do activate the innate system opened a new field that we will illustrate with a few examples. A lipid-based gene carrier which was supposed to be inert revealed immune-stimulatory activity, as evidenced by cytokine secretion (TNF-α, IL-12, IFN-β, ).Preliminary data showed that E.Coli cardiolipin activated the inflammatory responses whereas heart cardiolipin did not. These two types of cardiolipin differ exclusively by the degree acyl chain saturation. Cardiolipin from heart is largely unsaturated. Our experimental and modelling data provide evidence that acyl chain saturation is indeed a requirement for insertion into TLR binding pocket and explains the strong inflammatory activity of bacterial cardiolipin. An improved knowledge of the relationship between the lipid properties(nature of the hydrophilic moieties, hydrocarbon tails, mode of organisation) and the activation of the innate pathways opens the way to the design of new molecules tailored for specific applications in human cells (gene transport, adjuvant) and to therapeutic perspectives largely unintended until now. Lonez, C., Vandenbranden, M., and Ruysschaert, J. M. (2012) Adv. Drug Deliv. Rev. 64, 1749- 1758

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