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

Interferon regulatory factor 1-deficient (IRF-1(−/−)) mice infected with virulent Brucella abortus 2308 at 5 × 10(5) 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 × 10(5) 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 × 10(5)CFU 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.