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Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery
Monday Speaker Abstracts
17
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