COMPARISON OF RESISTANCE AND PATHOLOGIC CHANGES IN THE LUNG AMONG VARIOUS MOUSE STRAINS AFTER INFECTION WITH MYCOBACTERIUM TUBERCULOSIS H37RV

Five inbred strains of mice were examined for resistance to intravenous infection with 10^5 colony-forming units of Mycobacterium tuberculosis H37Rv. Based on the difference in survival time, five strains were classified into two groups : susceptible (CBA and DBA/2) and resistant (BALB/c, A/J, C57BL/6) strains. After infection with M. tuberculosis, mycobacteria rapidly multiplied in the lung with low levels of pulmonary IL- 12 production in CBA mice ; resulting in the progression of necrotic pneumonia. In contrast, mycobacteria slowly multiplied in association with high levels of IL-12 production in the lung of C57BL/6 mice ; leading to the development of granulomas. In C57BL/6 mice, the growth of bacteria was suppressed over a long period (6th-24th weeks) after infection, and granulomatous response in the lung was followed by progressive fibrosis capable of prevent- ing bacterial dissemination. When alveolar macrophages from both strains were infected in vitro with M. tuberculosis at a ratio of 1 : 10, the degree of phagocytic activity was not different between two strains, but C57BL/6 cells displayed higher anti-mycobacterial activity compared to CBA cells. These results suggest that murine natural resistance against M. tuberculosis depends on the anti-mycobacterial activity of alveolar macrophages, and the early production of IL-12 in the lung upon infection appears to be associated with the innate resistance and subsequent induction of M. tuberculosis-specific immunity. Moreover, vaccination with BCG was effective in reducing bacterial growth in both mouse strains during the initial phase of infection, while its effect was expressed in only resistant mice as the retardation of histopathologic progression during the late phase