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

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• 作者：Masato Kono^a ; Yutaro Nakamura^a ; ^{nakayuta@hama-med.ac.jp} ; Takafumi Suda^a ; Masato Uchijima^b ; Kunio Tsujimura^b ; Toshi Nagata^c ; Adam S. Giermasz^d ; Pawel Kalinski^e ; Hirotoshi Nakamura^a ; Kingo Chida^a
• 关键词：Dendritic cell ; Vaccine ; IL-12 ; Intracellular pathogen ; Listeria monocytogenes
• 刊名：Vaccine
• 出版年：2012
• 期刊代码：89_0264410x
• 类别：imm
• 出版时间：30 March, 2012
• 卷：30
• 期：16
• 页码：2633-2639
• 文件大小：644 K

摘要

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 鈥淒C exhaustion鈥?could be prevented by the presence of IL-4 and IFN-纬 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-纬 (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 na茂ve 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-纬 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.