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Infection and Immunity, May 2009, p. 2010-2021, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01322-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

T Cells from Lungs and Livers of Francisella tularensis-Immune Mice Control the Growth of Intracellular Bacteria{triangledown}

Carmen M. Collazo,1,{dagger} Anda I. Meierovics,1,{dagger} Roberto De Pascalis,1 Terry H. Wu,2 C. Rick Lyons,2 and Karen L. Elkins1*

Laboratory of Mycobacterial Diseases and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Rockville, Maryland 20852,1 Department of Internal Medicine, University of New Mexico Health Science Center, MSC10 5550, Albuquerque, New Mexico 871312

Received 30 October 2008/ Accepted 15 February 2009

Parenteral and respiratory vaccinations with the intracellular bacterium Francisella tularensis have been studied using the live vaccine strain (LVS) in a mouse model, and spleen cells from immune mice are often used for immunological studies. However, mechanisms of host immunological responses may be different in nonlymphoid organs that are important sites of infection, such as lung and liver. Using parenteral (intradermal) or respiratory (cloud aerosol) vaccination, here we examine the functions of resulting LVS-immune liver or lung cells, respectively. Surprisingly, LVS was considerably more virulent when administered by cloud aerosol than by intranasal instillation, suggesting method-dependent differences in initial localization and/or dissemination patterns. Only low doses were sublethal, and resolution of sublethal cloud aerosol infection was dependent on gamma interferon (IFN-{gamma}), tumor necrosis factor alpha, and inducible nitric oxide synthase. Nonetheless, survival of cloud aerosol or parenteral infection resulted in the development of a protective immune response against lethal LVS intraperitoneal or aerosol challenge, reflecting development of systemic secondary immunity in both cases. Such immunity was further detected by directly examining the functions of LVS-immune lung or liver lymphocytes in vitro. Lung lymphocytes primed by respiratory infection, as well as liver lymphocytes primed by parenteral infection, clearly controlled in vitro intracellular bacterial growth primarily via mechanisms that were not dependent on IFN-{gamma} activity. Thus, our results indicate functional similarities between immune T cells residing in spleens, livers, and lungs of LVS-immune mice.

* Corresponding author. Mailing address: 1401 Rockville Pike, HFM-431, Rockville, MD 20852. Phone: (301) 496-0544. Fax: (301) 435-5675. E-mail: karen.elkins{at}fda.hhs.gov

{triangledown} Published ahead of print on 23 February 2009.

Editor: W. A. Petri, Jr.

{dagger} C.M.C. and A.I.M. contributed equally to this study.

Infection and Immunity, May 2009, p. 2010-2021, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01322-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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