Genetic control of resistance to Mycobacterium intracellulare infection in mice

The susceptibilities of various strains of mice to a highly pathogenic strain of Mycobacterium intracellulare, the Mino strain, were determined by intravenous injection of 5 X 10(6) bacteria. CFU were counted on days 1 and 21 of infection. Among 10 strains of mice, C57BL/6, C57BL/10, BALB/c, B10.BR, B10.A, and B10.D2 were susceptible, whereas DBA/2, A/J, CBA, and C3H/He were resistant. In the susceptible mouse strains, the number of bacteria increased during 21 days of infection, whereas no bacterial growth was observed in the resistant strains. Susceptible mice showed weak but positive delayed-type hypersensitivity to M. intracellulare purified protein derivative 20 days after injection of bacteria. Resistant mice developed no delayed-type hypersensitivity. Histological examination showed severe granulomatous lesions in livers or spleens of the susceptible mice after M. intracellulare injection. Analysis of F1 hybrids of susceptible and resistant strains and of F2 and backcross mice showed that the resistance to M. intracellulare seems to be controlled genetically by a single dominant gene. The pattern of distribution of resistance to M. intracellulare among the mouse strains was consistent with that of natural resistance to Mycobacterium bovis to BCG. Thus, resistance to M. intracellulare infection may be regulated by a gene linked to the Bcg gene on chromosome 1.