Immunopathology of BCG infection in genetically resistant and susceptible mouse strains

Natural resistance to Mycobacterium bovis (BCG) is under the control of a single gene, designated Bcg. Resistant (Bcgr) mice prevent multiplication of an i.v. injected inoculum of congruent to 10(4) dispersed BCG cells, whereas progressive multiplication of this pathogen occurs in the first 3 wk of infection in spleens and livers of susceptible (Bcgs) mice. Striking differences in the development of cellular immunity, as measured by granuloma formation in the liver and spleen, delayed-typed hypersensitivity, and a resistance to the challenge with homologous (BCG) and heterologous (Listeria monocytogenes) pathogens, were detected between Bcgr (C3H/HeN and A/J) and Bcgs (C57BL/6J and B10.A) strains. Cellular immune reactions progressively developed in the Bcgs mice, as a response to the increasing bacterial load, whereas greatly inferior levels of acquired immunity were observed in Bcgr strains. These findings support the concept that mice genetically resistant to BCG infection are able to prevent bacterial multiplication without the need for a cellular immune response, whereas genetically susceptible mice will eventually control bacterial multiplication with the acquisition of cellular immunity.