EXPRESSION OF VIRULENCE OF MYCOBACTERIUM-TUBERCULOSIS WITHIN HUMAN MONOCYTES - VIRULENCE CORRELATES WITH INTRACELLULAR GROWTH AND INDUCTIONOF TUMOR-NECROSIS-FACTOR-ALPHA BUT NOT WITH EVASION OF LYMPHOCYTE-DEPENDENT MONOCYTE EFFECTOR FUNCTIONS

We assessed the applicability of an in vitro model of low-level infect ion of human monocytes to the characterization of the virulence of str ains of the Mycobacterium tuberculosis family. Peripheral blood monocy tes were infected at a 1:1 ratio with the virulent M. tuberculosis str ain H37Rv, the avirulent M. tuberculosis strain H37Ra, and the attenua ted M. bovis strain BCG. Both the percentages of cells infected by the three strains and the initial numbers of intracellular organisms were equivalent, as were level of monocyte viability up to 7 days followin g infection. Intracellular growth reflected virulence, as H37Rv replic ated in logarithmic fashion throughout the assay, BCG growth reached a plateau at 4 days, and H37Ra did not grow at all. The same patterns o f growth were observed following infection of human alveolar macrophag es with H37Rv and H37Ra. Monocyte production of tumor necrosis factor alpha was significantly higher following infection with virulent H37Rv than with either BCG or H37Ra. In contrast, there was no clear correl ation of interleukin 10 production with virulence. Nonadherent cells o f purified-protein-derivative-positive donors mediated equivalent degr ees of reduction of the intracellular growth of H37Rv, BCG, and H37Ra. Low-level infection of human monocytes with H37Rv, BCG, and H37Ra thu s provides an in vitro model for assessment of the virulence of these M. tuberculosis family strains. Furthermore, it is suggested that the virulence of these strains is expressed primarily by their differing a bilities to adapt to the intracellular environment of the mononuclear phagocyte.