Natural mycobacteriostatic activity in human monocyte-derived adherent cells

The effects of human monocyte maturity on the replication of virulent Mycobacterium tuberculosis were examined. Mycobacteria grew readily in freshly isolated, adherent peripheral blood monocytes and in monocyte-derived macrophages obtained after 7 days in culture, as measured by counts of acid-fast bacilli and colony-forming units. Monocytes cultured for only 3 days before infection, however, were less permissive for the mycobacteria than either uncultured or 7-day cells. The association between the low permissiveness of 3-day cells and superoxide production was examined. Mycobacteria induced only a slight increase in superoxide production during the first 60 min of infection in uncultured and in 3-day cells, and no increase in cells cultured for 7 days before infection. Freshly isolated adherent cells produced small amounts of superoxide in response to phorbol myristate acetate (PMA) stimulation, but PMA-induced superoxide production increased steadily for 7 days. Mycobacteria had no effect on superoxide production by PMA-stimulated adherent cells. These results suggest that the suppressive activity of the 3-day cells is not associated with the production of increased amounts of reactive oxygen species.