Effective Induction of Acquired Resistance to Listeria monocytogenes by Immunizing Mice with In Vivo-Infected Dendritic Cells
Department of Bacteriology,1 Second Department of Surgery, Hirosaki University School of Medicine, Hirosaki,3 Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan2%3;^}9/, 百拇医药
Received 29 August 2002/ Accepted 22 October 2002%3;^}9/, 百拇医药
ABSTRACT%3;^}9/, 百拇医药
Splenic dendritic cells (DCs) obtained from mice at 48 h after Listeria monocytogenes infection exhibited up-regulation of CD80 and produced higher titers of gamma interferon (IFN-) and interleukin-12 (IL-12) than did DCs obtained from uninfected mice. Mice immunized with DCs obtained from mice that had been infected with L. monocytogenes 48 h before acquired host resistance to lethal infection with L. monocytogenes at 4 and 8 weeks. Immunization with DCs from heat-killed L. monocytogenes failed to induce resistance. Acquired antilisterial resistance is specific, since the immunized mice could not be protected from Salmonella enterica serovar Typhimurium infection. Infected DCs stimulated proliferation of naive CD4+ and CD8+ cells in vitro, suggesting that in vivo-infected DCs activate CD8+ T cells, which are critical in acquired antilisterial resistance, as well as CD4+ T cells. When wild-type mice were immunized with DCs from IFN--deficient mice, they were protected against a lethal L. monocytogenes challenge. In contrast, when mice were immunized with DCs from anti-IL-12 p40 monoclonal antibody-injected mice, they failed to gain acquired antilisterial resistance. These results suggest that DC-derived IL-12, but not IFN-, may play a critical role in induction of acquired antilisterial resistance. Our present results suggest that splenic DCs obtained from mice infected with L. monocytogenes in vivo may be an effective immunogen with which to induce antigen-specific immunity.%3;^}9/, 百拇医药
INTRODUCTION%3;^}9/, 百拇医药
The dendritic cell (DC) is a major antigen-presenting cell, and DCs efficiently activate T cells. Immature DCs are resident in the peripheral tissues and circulate in the bloodstream. When immature DCs encounter antigens, these cells take them up by phagocytosis and migrate to regional lymph nodes via afferent lymphatic vessels. In the regional lymph nodes, immature DCs mature and activate naive T cells (2). Mature DCs can produce cytokines, including interleukin-12 (IL-12), IL-18, tumor necrosis factor alpha, gamma interferon (IFN-), and IFN-(Hiroshi Sashinami Akio Nakane Yoichiro Iwakura and Mutsuo Sasaki)
Received 29 August 2002/ Accepted 22 October 2002%3;^}9/, 百拇医药
ABSTRACT%3;^}9/, 百拇医药
Splenic dendritic cells (DCs) obtained from mice at 48 h after Listeria monocytogenes infection exhibited up-regulation of CD80 and produced higher titers of gamma interferon (IFN-) and interleukin-12 (IL-12) than did DCs obtained from uninfected mice. Mice immunized with DCs obtained from mice that had been infected with L. monocytogenes 48 h before acquired host resistance to lethal infection with L. monocytogenes at 4 and 8 weeks. Immunization with DCs from heat-killed L. monocytogenes failed to induce resistance. Acquired antilisterial resistance is specific, since the immunized mice could not be protected from Salmonella enterica serovar Typhimurium infection. Infected DCs stimulated proliferation of naive CD4+ and CD8+ cells in vitro, suggesting that in vivo-infected DCs activate CD8+ T cells, which are critical in acquired antilisterial resistance, as well as CD4+ T cells. When wild-type mice were immunized with DCs from IFN--deficient mice, they were protected against a lethal L. monocytogenes challenge. In contrast, when mice were immunized with DCs from anti-IL-12 p40 monoclonal antibody-injected mice, they failed to gain acquired antilisterial resistance. These results suggest that DC-derived IL-12, but not IFN-, may play a critical role in induction of acquired antilisterial resistance. Our present results suggest that splenic DCs obtained from mice infected with L. monocytogenes in vivo may be an effective immunogen with which to induce antigen-specific immunity.%3;^}9/, 百拇医药
INTRODUCTION%3;^}9/, 百拇医药
The dendritic cell (DC) is a major antigen-presenting cell, and DCs efficiently activate T cells. Immature DCs are resident in the peripheral tissues and circulate in the bloodstream. When immature DCs encounter antigens, these cells take them up by phagocytosis and migrate to regional lymph nodes via afferent lymphatic vessels. In the regional lymph nodes, immature DCs mature and activate naive T cells (2). Mature DCs can produce cytokines, including interleukin-12 (IL-12), IL-18, tumor necrosis factor alpha, gamma interferon (IFN-), and IFN-(Hiroshi Sashinami Akio Nakane Yoichiro Iwakura and Mutsuo Sasaki)