title: Cationic lipid nanocarriers activate Toll-like receptor 2 and NLRP3 inflammasome pathways.
abstract: We provide evidence that cationic lipids, usually considered as a safe alternative to viral vectors as nanocarriers for gene therapy or drug intracellular delivery, do not behave as inert material but do activate cellular signalling pathways implicated in inflammatory reactions. We show here that the cationic lipid RPR206252 induces NF-κB activation, and the production of TNF-α, IL-1β, IL-6 and IFN-γ by human or mouse macrophage cell lines. Further, we demonstrate that the activation of inflammatory cascades by RPR206252 is dependent on Toll-like receptor 2 (TLR2), the natural sensor of bacterial lipopeptides and NOD-like receptor protein 3 (NLRP3), the major inflammasome component. Our results suggest that cationic lipid nanocarriers because of their ability to stimulate the innate system can be used as a new class of synthetic and safe adjuvant for vaccination.
  
  
  BACKGROUND
  Cationic lipid nanocarriers are typically considered neutral tools for gene delivery. However, as demonstrated in this study, they possess a clear ability to stimulate the innate immune system, and actually can be used as a new class of synthetic and safe adjuvant for vaccination.
authors.affiliation: Structure and Function of Biological Membranes, Université Libre de Bruxelles, Belgium; Department of Veterinary Medicine, The University of Cambridge, United Kingdom. Electronic address: clonez@ulb.ac.be.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lonez
authors.affiliation: Laboratoire de Pharmacologie Chimique et Génétique et d'Imagerie, CNRS UMR8151, Inserm U1022, Université René Descartes - Chimie ParisTech, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Bessodes
authors.affiliation: Laboratoire de Pharmacologie Chimique et Génétique et d'Imagerie, CNRS UMR8151, Inserm U1022, Université René Descartes - Chimie ParisTech, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Scherman
authors.affiliation: Structure and Function of Biological Membranes, Université Libre de Bruxelles, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Vandenbranden
authors.affiliation: Laboratoire de Pharmacologie Chimique et Génétique et d'Imagerie, CNRS UMR8151, Inserm U1022, Université René Descartes - Chimie ParisTech, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Escriou
authors.affiliation: Structure and Function of Biological Membranes, Université Libre de Bruxelles, Belgium.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Ruysschaert
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D053758:Nanoparticles; D051195:Toll-Like Receptor 2 / Q000276:immunology*
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D004337:Drug Carriers; D008055:Lipids; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C492716:Nlrp3 protein, mouse; C495342:TLR2 protein, human; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2
keywords: Cationic lipids; Immunostimulatory properties; Innate system; NLRP3; Toll-like receptor 2