Interferon-gamma Is Crucial for Surviving a Brucella Abortus Infection in Both Resistant C57BL/6 and Susceptible BALB/c Mice

Immunology. 2001 Aug;103(4):511-8. doi: 10.1046/j.1365-2567.2001.01258.x.

Abstract

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-gamma (IFN-gamma), perforin or beta(2)-microglobulin genes had decreased abilities to control intracellular infections with B. abortus strain 2308 during the first week after infection. However, only the IFN-gamma 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-gamma 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-gamma 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-gamma gene disrupted mice coincided with symptoms of cachexia and macrophages comprised > or= 75% of the splenic leucocytes.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brucella abortus*
  • Brucellosis / immunology*
  • Disease Susceptibility
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology*
  • Interleukin-12 / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Spleen / immunology

Substances

  • Interleukin-12
  • Interferon-gamma