A mouse model of the recrudescence of latent tuberculosis in the elderly

Abstract

The present study was designed to attempt to construct an animal model of the recrudescence of pulmonary tuberculosis by following the course of infection in mice exposed at 3 months of age to a low dose aerosol of Mycobacterium tuberculosis Erdman. The results show that such mice died of overwhelming lung disease at a median age of 24 months; in contrast, uninfected mice lived 4 to 6 months longer. Examination of infected mice over the period of 20 to 24 months of age provided evidence to suggest that recrudescence over this period of time was a general phenomenon within the infected mice, and was characterized by increases in lung bacterial numbers from approximately 10(4) to 10(8) organisms per animal. Experiments designed to investigate the underlying basis of this recrudescence revealed that the capacity of the old mice to mount acquired immunity to the infection exhibited a substantial age-related decline in these animals when compared with young mice exposed to similar aerogenic doses. The data suggest, therefore, that "spontaneous" recrudescence of pulmonary tuberculosis in old mice reflects their inability to recall anamnestic acquired immunity to the reemerging infection.