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Infection and Immunity, December 2002, p. 7004-7012, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.7004-7012.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Virulence Criteria for Brucella abortus Strains as Determined by Interferon Regulatory Factor 1-Deficient Mice

Jinkyung Ko,1 Annette Gendron-Fitzpatrick,2 Thomas A. Ficht,3 and Gary A. Splitter1*

Laboratory of Cellular and Molecular Immunology, Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison, Wisconsin 53706,1 Research Animal Resource Center, University of Wisconsin, Madison, Wisconsin 53705,2 Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University and Texas Agricultural Experiment Station, College Station, Texas 778433

Received 21 March 2002/ Returned for modification 2 July 2002/ Accepted 12 August 2002

Interferon regulatory factor 1-deficient (IRF-1-/-) mice infected with virulent Brucella abortus 2308 at 5 x 105 CFU developed acute hepatitis similar to many natural hosts but, unlike natural hosts, IRF-1-/- mice were unable to resolve infection and died. In contrast, IRF-1-/- mice survived when infected at 5 x 105 CFU with several attenuated Brucella strains (S19, RB51, cbp, and cyd). The survival of infected IRF-1-/- mice is likely a function of the level of virulence of each Brucella strain and the extent of retained immunity. Further, these findings suggest that adaptive immunity may be important to the survival of IRF-1-/- mice since attenuated Brucella strains can protect IRF-1-/- mice against lethal challenge with virulent Brucella. Using the IRF-1-/- mouse model, the following set of criteria were identified to define Brucella virulence: (i) the day of death for 50% of mice infected with 5 x 105CFU of Brucella, (ii) the extent of liver toxicity, and (iii) the minimum immunizing dose of Brucella to protect against challenge with virulent S2308. Thus, IRF-1-/- mice are important to determining the level of Brucella virulence, to evaluating Brucella mutants for attenuation, and to investigating adaptive immunity in brucellosis.

* Corresponding author. Mailing address: Laboratory of Cellular and Molecular Immunology, Department of Animal Health and Biomedical Sciences, 1656 Linden Dr., University of Wisconsin, Madison, WI 53706. Phone: (608) 262-1837. Fax: (608) 262-7420. E-mail: splitter{at}ahabs.wisc.edu.

Editor: V. J. DiRita

Infection and Immunity, December 2002, p. 7004-7012, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.7004-7012.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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