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Infection and Immunity, January 2003, p. 117-125, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.117-125.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Effective Induction of Acquired Resistance to Listeria monocytogenes by Immunizing Mice with In Vivo-Infected Dendritic Cells

Hiroshi Sashinami,1 Akio Nakane,1* Yoichiro Iwakura,2 and Mutsuo Sasaki3

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

Received 29 August 2002/ Accepted 22 October 2002

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-{gamma}) 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-{gamma}-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-{gamma}, 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.

* Corresponding author. Mailing address: Department of Bacteriology, Hirosaki University School of Medicine, Zaifu-cho 5, Hirosaki, Aomori 036-8562, Japan. Phone: 81-172-39-5032. Fax: 81-172-39-5034. E-mail: a27k03n0{at}cc.hirosaki-u.ac.jp.

Editor: J. D. Clements

Infection and Immunity, January 2003, p. 117-125, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.117-125.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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