title: Nanoemulsion nasal adjuvant W₈₀5EC induces dendritic cell engulfment of antigen-primed epithelial cells.
abstract: Nanoemulsions are adjuvants that enhance antigen penetration in the nasal mucosa, increase cellular uptake of antigens by both epithelial dendritic cells, and promote migration of antigen-loaded dendritic cells to regional lymph nodes within a day of vaccine administration. The objective of this study was to determine whether the W(80)5EC nanoemulsion adjuvant enhances immune response not only by direct uptake of antigen by dendritic cells, but also indirectly, by phagocytosis of antigen-primed, apoptotic, epithelial cells. Consistent with this, we show that exposure of both epithelial cells (TC-1s) and dendritic cells (JAWS II or bone marrow derived dendritic cells (BMDCs)) to nanoemulsion exhibited augmented antigen uptake in cell culture. TC-1 cells subsequently underwent G(2)/M cell cycle arrest and apoptosis, and when co-cultured with JAWS II or BMDCs were rapidly engulfed by the dendritic cells, which responded by up-regulating dendritic cell maturation marker CD86. Altogether these results suggest that the effectiveness of nanoemulsions as adjuvants stems, at least in part, from the engulfment of antigen-loaded epithelial cells, leading to enhanced antigen processing and a strong and balanced mucosal and systemic immune response.
authors.affiliation: Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI 48109-0648, United States. myca@umich.edu
authors.forename: Andrzej
authors.initials: A
authors.lastname: Myc
authors.forename: Jolanta F
authors.initials: JF
authors.lastname: Kukowska-Latallo
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Smith
authors.forename: Crystal
authors.initials: C
authors.lastname: Passmore
authors.forename: Tiffany
authors.initials: T
authors.lastname: Pham
authors.forename: Pamela
authors.initials: P
authors.lastname: Wong
authors.forename: Anna U
authors.initials: AU
authors.lastname: Bielinska
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000818:Animals; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D004655:Emulsions / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000187:drug effects*
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D004655:Emulsions