title: Enhancement of protective immunity against intracellular bacteria using type-1 polarized dendritic cell (DC) vaccine.
abstract: The development of effective vaccine strategies for intracellular bacteria, including tuberculosis, is one of the major frontiers of medical research. Our previous studies showed that dendritic cell (DC) vaccine is a promising approach for eliciting protective immunity against intracellular bacteria. However, it has been reported that standard fully mature DCs show reduced ability to produce IL-12p70 upon subsequent interaction with antigen (Ag)-specific T cells, limiting their in vivo performance for vaccines. Recently, we found that such "DC exhaustion" could be prevented by the presence of IL-4 and IFN-γ during the maturation of mouse DCs (type-1 polarization), resulting in improved induction of anti-tumor immunity in cancer. Here we show that such type-1 polarized DCs promote dramatic enhancement of protective immunity against an intracellular bacterium, Listeria monocytogenes. Murine bone marrow-derived DCs were cultured and matured with LPS, IL-4 and IFN-γ (type-1 polarized DCs), and with LPS alone (non-polarized DCs). DCs were loaded with listeriolysin O (LLO) 91-99, H2-K(d)-restricted epitope of L. monocytogenes, and were injected into naïve BALB/c mice intravenously. Type-1 polarized DCs produced significantly higher levels of IL-12p70 than non-polarized DCs in vitro, and this vaccine strongly enhanced LLO 91-99-specific CD8(+) T cells exhibiting epitope-specific cytotoxic activity and IFN-γ production, leading to significant induction of protective immunity against L. monocytogenes. Type-1 polarized DCs are potential candidates for enhancing protective immunity in the design of effective vaccination strategies against intracellular bacteria.
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kono
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suda
authors.forename: Masato
authors.initials: M
authors.lastname: Uchijima
authors.forename: Kunio
authors.initials: K
authors.lastname: Tsujimura
authors.forename: Toshi
authors.initials: T
authors.lastname: Nagata
authors.forename: Adam S
authors.initials: AS
authors.lastname: Giermasz
authors.forename: Pawel
authors.initials: P
authors.lastname: Kalinski
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Kingo
authors.initials: K
authors.lastname: Chida
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology*; D006460:Hemolysin Proteins / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D014611:Vaccination
chemical_list: D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D008070:Lipopolysaccharides; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; C038705:hlyA protein, Listeria monocytogenes