Interferon-gamma is crucial for surviving a Brucella abortus infection in both resistant C57BL/6 and susceptible BALB/c mice.
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.
Murphy
E A
EA
Department of Veterinary and Animal Sciences, Paige Laboratory, University of Massachusetts, Amherst, MA 01003, USA.
Sathiyaseelan
J
J
Parent
M A
MA
Zou
B
B
Baldwin
C L
CL
D000818:Animals; D002003:Brucella abortus; D002006:Brucellosis / Q000276:immunology*; D004198:Disease Susceptibility; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D018664:Interleukin-12 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology
D018664:Interleukin-12; D007371:Interferon-gamma