Outcome and immune responses after Brucella abortus infection in young adult and aged mice

Abstract

Aging results in a general waning of immunity and enhanced susceptibility to many intracellular pathogens. However, in some instances, aging is accompanied by alternative immune responses that can be equal to, or even more effective, than those of young adults. Brucella spp. are intracellular bacteria and important human and animal pathogens, but there are no data regarding the effect of age on host defense in brucellosis. Young or old adult mice (DBA/2 or BALB/c) were infected with either an attenuated B. abortus strain that over-expressed the Brucella superoxide dismutase (strain RB51-SOD) or a fully virulent strain (strain 2308). Survival, organism burden in the spleen, and immune responses were assessed. All young adult and aged mice survived infection with RB51-SOD (up to 6 x 10(8) cfu) or strain 2308 (up to 8 x 10(8) cfu). Old mice had a lower organism burden in the spleen than young adult mice five or more weeks after infection. Antibody and cytokine responses were Th1-focused in young adult mice, but Th-mixed in older mice, including evidence of the newly defined Th17 subtype immune response. Immunization with the RB51-SOD strain provided protection vs. strain 2308 challenge in young and aged BALB/c, but only young adult DBA/2 mice. Thus, clinical outcomes of Brucella infection in aged mice are equal or superior to those of young adult mice; immune responses in older mice are less-Th1 specific suggesting alternate pathways may contribute to host defense vs. Brucella in aged mice.