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Infection and Immunity, April 2005, p. 2306-2311, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2306-2311.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Intranasal Interleukin-12 Treatment for Protection against Respiratory Infection with the Francisella tularensis Live Vaccine Strain

Nathalie S. Duckett, Sofia Olmos, Douglas M. Durrant, and Dennis W. Metzger*

Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York

Received 15 October 2004/ Returned for modification 29 November 2004/ Accepted 15 December 2004

Francisella tularensis is a gram-negative intracellular bacterium that can induce lethal respiratory infection in humans and rodents. However, little is known about the role of innate or adaptive immunity in protection from respiratory tularemia. In the present study, the role of interleukin-12 (IL-12) in inducing protective immunity in the lungs against intranasal infection of mice with the live vaccine strain (LVS) of F. tularensis was investigated. It was found that gamma interferon (IFN-{gamma}) and IL-12 were strictly required for protection, since mice deficient in IFN-{gamma}, IL-12 p35, or IL-12 p40 all succumbed to LVS doses that were sublethal for wild-type mice. Furthermore, exogenous IL-12 treatment 24 h before intranasal infection with a lethal dose of LVS (10,000 CFU) significantly decreased bacterial loads in the lungs, livers, and spleens of wild-type BALB/c and C57BL/6 mice and allowed the animals to survive infection; such protection was not observed in IFN-{gamma}-deficient mice. The resistance induced by IL-12 to LVS infection was still observed in NK cell-deficient beige mice but not in CD8–/– mice. These results demonstrate that exogenous IL-12 delivered intranasally can prevent respiratory tularemia through a mechanism that is at least partially dependent upon the expression of IFN-{gamma} and CD8 T cells.

* Corresponding author. Mailing address: Center for Immunology and Microbial Disease MC-151, Albany Medical College, 47 New Scotland Ave., Albany, NY 12208. Phone: (518) 262-6026. Fax: (518) 262-6053. E-mail: metzged{at}mail.amc.edu.

Editor: J. N. Weiser

Infection and Immunity, April 2005, p. 2306-2311, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2306-2311.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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