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Infection and Immunity, February 1999, p. 568-575, Vol. 67, No. 2
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Induction of Protective T Cells against Listeria monocytogenes in Mice by Immunization with a Listeriolysin O-Negative Avirulent Strain of Bacteria and Liposome-Encapsulated Listeriolysin O

Yoshinari Tanabe,1,2,* Huabao Xiong,1 Takamasa Nomura,1,3 Masaaki Arakawa,2 and Masao Mitsuyama1,3

Departments of Bacteriology1 and Internal Medicine (II),2 Niigata University School of Medicine, Niigata 951-8510, and Department of Microbiology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501,3 Japan

Received 8 June 1998/Returned for modification 15 July 1998/Accepted 19 November 1998

Only listeriolysin O (LLO)-producing strains of Listeria monocytogenes generate protective immunity in mice. Based on the findings that endogenous gamma interferon (IFN-gamma ) production was induced only by such strains and that purified LLO could induce IFN-gamma from NK cells, we have postulated that LLO may play a pivotal role in the induction of Th1-type protective T cells, which are highly dependent on IFN-gamma . In this study, mice were immunized with L. monocytogenes ATCC 15313, an LLO-nonproducing avirulent strain, along with LLO encapsulated in liposome (LLO-liposome). LLO-liposome was highly potent in the induction of various cytokines, including IFN-gamma . Immunization of mice with either LLO-liposome or the viable strain ATCC 15313 alone did not induce protection against challenge infection. In contrast, the combination of LLO-nonproducing bacteria plus LLO-liposome induced a significant level of protective immunity mediated mainly by Th1-type cells capable of producing a large amount of IFN-gamma in an antigen-specific manner. The protection afforded by the combination was not dependent on LLO-specific cytotoxic T cells. These results support the idea that the inability of an LLO-nonproducing avirulent strain or killed bacteria to induce the generation of protective T cells is due not to the lack of a central T-cell epitope(s) but to the lack of ability to induce the production of endogenous cytokine during the early stage of immunization; the results also suggest that an appropriate use of LLO at least in an animal model may be effective in the induction of antigen-specific Th1-dependent protective immunity to various kinds of intracellular parasitic bacteria.

* Corresponding author. Mailing address: Department of Internal Medicine, Nagaoka Red Cross Hospital, 297-1 Terashima-cho, Nagaoka, Niigata 940-2085, Japan. Phone: (81)258-28-3600. Fax: (81)258-28-9000. E-mail: ytanabe{at}med.niigata-u.ac.jp.

Infection and Immunity, February 1999, p. 568-575, Vol. 67, No. 2
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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