Differences in response among inbred mouse strains to infection with small doses of Mycobacterium bovis BCG

Intravenous infection of six inbred mouse strains with small doses of dispersed cells of Mycobacterium bovis BCG (15.5 x 10(3) or 15.5 x 10(4) colony-forming units) separated them into resistant (C3H/HeCr, A/J, and DBA/2) and sensitive (B10.A, C57BL/6, and BALB/c) strains as assessed by the magnitude of bacterial multiplication in the spleens at 28 days. The two groups were more sharply separated after infection with the lower dose of BCG (15.5 x 10(3) colony-forming units), which allowed for true multiplication of the bacteria in the spleens of permissive hosts, expressed as the ratio of the number of BCG recovered from the spleens to the number of BCG injected. This coefficient of increase was less than 1 in resistant strains, whereas it was higher than 2.5 in sensitive strains. Significant splenomegaly developed only in mice of the sensitive strains infected with BCG when compared with uninfected controls. There was no correlation between the magnitude of the delayed-type hypersensitivity (DTH) to BCG and susceptibility to infection: DTH was absent in both the sensitive and the resistant strains when the smaller dose of BCG was used for infection. Moreover, significant DTH was detected in animals of the most sensitive (BALB/c) as well as of the most resistant (C3H/HeCr) strain when the higher dose of BCG (15.5 x 10(4)) was used for immunization. These results document significant genetic differences in the ability of inbred mice to inhibit bacterial multiplication after infection with small dispersed doses of BCG. Resistance to BCG multiplication, in this model, does not appear to be related to the establishment of DTH.