Enhancement of protective immunity against intracellular bacteria using type-1 polarized dendritic cell (DC) vaccine

Masato Kono, Yutaro Nakamura, Takafumi Suda, Masato Uchijima, Kunio Tsujimura, Toshi Nagata, Adam Giermasz, Pawel Kalinski, Hirotoshi Nakamura, Kingo Chida

Research output: Contribution to journalArticle

19 Scopus citations

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-Kd-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.

Original languageEnglish (US)
Pages (from-to)2633-2639
Number of pages7
JournalVaccine
Volume30
Issue number16
DOIs
StatePublished - Mar 30 2012

Keywords

  • Dendritic cell
  • IL-12
  • Intracellular pathogen
  • Listeria monocytogenes
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

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    Kono, M., Nakamura, Y., Suda, T., Uchijima, M., Tsujimura, K., Nagata, T., Giermasz, A., Kalinski, P., Nakamura, H., & Chida, K. (2012). Enhancement of protective immunity against intracellular bacteria using type-1 polarized dendritic cell (DC) vaccine. Vaccine, 30(16), 2633-2639. https://doi.org/10.1016/j.vaccine.2012.02.026