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Infection and Immunity, March 2007, p. 1453-1462, Vol. 75, No. 3
0019-9567/07/$08.00+0     doi:10.1128/IAI.00274-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Protection against Cryptococcosis by Using a Murine Gamma Interferon-Producing Cryptococcus neoformans Strain{triangledown}

Floyd L. Wormley Jr.,1* John R. Perfect,2 Chad Steele,3 and Gary M. Cox2

Department of Biology, University of Texas at San Antonio, San Antonio, Texas,1 Department of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina,2 Department of Pediatrics, Division of Pulmonology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania3

Received 20 February 2006/ Returned for modification 25 March 2006/ Accepted 19 December 2006

We evaluated cell-mediated immune (CMI) responses in mice given a pulmonary infection with a Cryptococcus neoformans strain engineered to produce the Th1-type cytokine gamma interferon (IFN-{gamma}). Mice given a pulmonary infection with an IFN-{gamma}-producing C. neoformans strain were able to resolve the primary infection and demonstrated complete (100%) protection against a second pulmonary challenge with a pathogenic C. neoformans strain. Pulmonary cytokine analyses showed that Th1-type/proinflammatory cytokine and chemokine expression were significantly higher and Th2-type cytokine expression was significantly lower in mice infected with the IFN-{gamma}-producing C. neoformans strain compared to wild-type-infected mice. This increased pulmonary Th1-type cytokine expression was also associated with significantly lower pulmonary fungal burden and significantly higher pulmonary leukocyte and T-lymphocyte recruitment in mice infected with the IFN-{gamma}-producing C. neoformans strain compared to wild-type-infected mice. Our results demonstrate that pulmonary infection of mice with a C. neoformans strain expressing IFN-{gamma} results in the stimulation of local Th1-type anti-cryptococcal CMI responses and the development of protective host immunity against future pulmonary cryptococcal infections. The use of fungi engineered to produce host cytokines is a novel method to study immune responses to infection and may be useful in developing vaccine strategies in humans.

* Corresponding author. Mailing address: Department Biology, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249-0062. Phone: (210) 458-7020. Fax: (210) 458-7021. E-mail: floyd.wormley{at}utsa.edu.

{triangledown} Published ahead of print on 8 January 2007.

Editor: A. Casadevall

Infection and Immunity, March 2007, p. 1453-1462, Vol. 75, No. 3
0019-9567/07/$08.00+0     doi:10.1128/IAI.00274-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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