Interferon‐γ is crucial for surviving a Brucella abortus infection in both resistant C57BL/6 and susceptible BALB/c mice

Abstract

Summary Brucella abortus is an intracellular bacterial pathogen that causes chronic infections in humans and a number of agriculturally important species of animals. It has been shown that BALB/c mice are more susceptible to infections with virulent strains of Brucella abortus than C57BL/6 or C57BL/10 strains. In experiments described here, gene knock‐out mice were utilized to elucidate some of the salient components of resistance. Resistant C57BL/6 mice with gene deletions or disruptions in the interferon‐γ (IFN‐γ), perforin or β2‐microglobulin genes had decreased abilities to control intracellular infections with B. abortus strain 2308 during the first week after infection. However, only the IFN‐γ knock‐out mice had a sustained inability to control infections and this resulted in death of the mice at approximately 6 weeks post‐infection. These mice had a continual increase in the number of bacterial colony‐forming units (CFU) in their spleens until death. When BALB/c mice with the disrupted IFN‐γ gene were infected they had more splenic CFU at one week post‐infection than control mice but the increase was not statistically significant and by 3 weeks they did not have more CFU than control mice. Moreover, the number of splenic bacteria did not increase in the BALB/c IFN‐γ knock‐out mice between 6 and 10·5 weeks, although they died at 10·5 weeks, the time by which normal BALB/c mice were clearing the infection. Death in both strains of IFN‐γ gene disrupted mice coincided with symptoms of cachexia and macrophages comprised ≥ 75% of the splenic leucocytes.