DECREASED CAPACITY OF AGED MICE TO PRODUCE INTERFERON-GAMMA IN LEGIONELLA-PNEUMOPHILA INFECTION

We investigated the difference in natural resistance to Legionella pne umophila infection between aged (18-20-month-old) and young (3-month-o ld) mice of ddY strain. Aged mice were more susceptible to the bacteri al infection than young mice; 50% lethal doses of L. pneumophila for a ged and young mice were 2.2 x 10(7) and 8.5 x 10(7) colony forming uni ts (CFU), respectively, after intraperitoneal injection of the bacteri a. The bacterial burden in the livers was larger in aged than young mi ce after a challenge with a sublethal dose of L. pneumophila. However, peritoneal macrophages of aged mice paradoxically had a greater capac ity to kill intracellular L. pneumophila than those of young mice. Int erferon-gamma (IFN-gamma) production from naive spleen cells was compa red after an in vitro stimulation with formalin-killed L. pneumophila. Spleen cells of aged mice produced significantly less IFN-gamma than those of young mice. When anti-murine IFN-gamma monoclonal antibody wa s administered before the bacterial infection, the subsequent bacteria l burden in the livers significantly increased in young but not in age d mice. These data suggest that, in aged mice, IFN-gamma production is depressed at an early phase of L. pneumophila infection and it render s aged mice more susceptible to the infection.