title: Archaeosomes varying in lipid composition differ in receptor-mediated endocytosis and differentially adjuvant immune responses to entrapped antigen.
abstract: Archaeosomes prepared from total polar lipids extracted from six archaeal species with divergent lipid compositions had the capacity to deliver antigen for presentation via both MHC class I and class II pathways. Lipid extracts from Halobacterium halobium and from Halococcus morrhuae strains 14039 and 16008 contained archaetidylglycerol methylphosphate and sulfated glycolipids rich in mannose residues, and lacked archaetidylserine, whereas the opposite was found in Methanobrevibacter smithii, Methanosarcina mazei and Methanococcus jannaschii. Annexin V labeling revealed a surface orientation of phosphoserine head groups in M. smithii, M. mazei and M. jannaschii archaeosomes. Uptake of rhodamine-labeled M. smithii or M. jannaschii archaeosomes by murine peritoneal macrophages was inhibited by unlabeled liposomes containing phosphatidylserine, by the sulfhydryl inhibitor N-ethylmaleimide, and by ATP depletion using azide plus fluoride, but not by H. halobium archaeosomes. In contrast, N-ethylmaleimide failed to inhibit uptake of the four other rhodamine-labeled archaeosome types, and azide plus fluoride did not inhibit uptake of H. halobium or H. morrhuae archaeosomes. These results suggest endocytosis of archaeosomes rich in surface-exposed phosphoserine head groups via a phosphatidylserine receptor, and energy-independent surface adsorption of certain other archaeosome composition classes. Lipid composition affected not only the endocytic mechanism, but also served to differentially modulate the activation of dendritic cells. The induction of IL-12 secretion from dendritic cells exposed to H. morrhuae 14039 archaeosomes was striking compared with cells exposed to archaeosomes from 16008. Thus, archaeosome types uniquely modulate antigen delivery and dendritic cell activation.
authors.affiliation: Institute for Biological Sciences, National Research Council, 100 Sussex Drive, Ottawa, Ontario, Canada K1A 0R6. dennis.sprott@nrc.ca
authors.forename: G Dennis
authors.initials: GD
authors.lastname: Sprott
authors.forename: Subash
authors.initials: S
authors.lastname: Sad
authors.forename: L Perry
authors.initials: LP
authors.lastname: Fleming
authors.forename: Chantal J
authors.initials: CJ
authors.lastname: Dicaire
authors.forename: Girishchandra B
authors.initials: GB
authors.lastname: Patel
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Krishnan
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D001105:Archaea / Q000737:chemistry / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004705:Endocytosis; D005260:Female; D008055:Lipids / Q000737:chemistry / Q000276:immunology; D008081:Liposomes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D010047:Ovalbumin / Q000276:immunology; D010587:Phagocytosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D016339:Spectrometry, Mass, Fast Atom Bombardment
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D008055:Lipids; D008081:Liposomes; C498708:Ptdsr protein, mouse; D011956:Receptors, Cell Surface; C408123:phosphatidylserine receptor; D010047:Ovalbumin