title: Lipopolysaccharide-QD micelles induce marked induction of TLR2 and lipid droplet accumulation in olfactory bulb microglia.
abstract: The intranasal entry of biological and artificial nanoparticles can induce inflammatory responses both locally and more widely in surrounding tissues. The aim of this study was to assess the microglia activation induced by nanoparticles with different surfaces in (i) a transgenic mouse (Toll-like receptor (TLR)-2-luciferase (Luc) reporter) which allowed the biophotonic imaging of microglial activation/innate immune response after intranasal delivery of nanoparticles and (ii) in microglial dispersed cells in vitro. Cadmium selenide nanoparticles (quantum dots, QD), surface-exchanged with lipopolysaccharide (LPS) to form micelles, were tested to assess microglia activation and lipid droplet formation in both model systems. In vivo imaging revealed a robust increase in the extent of microglial activation/TLR2 response, initially in the olfactory bulb, but also in other more caudal brain regions. The increased TLR2 expression was complemented with enhanced CD68 expression in activated microglia in the same regions. Intense in vitro microglial activation by LPS-QD micelles was accompanied by a significant enhancement of nitric oxide production and formation of large lipid droplets, suggesting the possibility of this organelle acting as an inflammatory biomarker in response to nanoparticles, and not simply as a storage site in fat tissues.
authors.affiliation: Department of Psychiatry and Neuroscience, Centre de Recherche du CHUL, Faculty of Medicine, Laval University, Quebec, QC, Canada.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Lalancette-Hébert
authors.forename: Alexandre
authors.initials: A
authors.lastname: Moquin
authors.forename: Angela O
authors.initials: AO
authors.lastname: Choi
authors.forename: Jasna
authors.initials: J
authors.lastname: Kriz
authors.forename: Dusica
authors.initials: D
authors.lastname: Maysinger
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D019187:Cadmium Compounds / Q000737:chemistry; D002460:Cell Line; D007150:Immunohistochemistry; D050356:Lipid Metabolism / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D008823:Micelles; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009569:Nitric Oxide / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology*; D018036:Selenium Compounds / Q000737:chemistry; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019187:Cadmium Compounds; D008070:Lipopolysaccharides; D008823:Micelles; D009569:Nitric Oxide; D018036:Selenium Compounds; D051195:Toll-Like Receptor 2; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C058667:cadmium selenide