Hydrogen peroxide and superoxide production by peripheral blood monocytes in leprosy.

Susceptibility to infection with Mycobacterium leprae, the causative organism of leprosy, is the result of a defect in cell-mediated immunity (CMI). The co-operation of macrophages and T lymphocytes is known to be essential for competent CMI response. In this study we have examined peripheral blood monocytes from a range of leprosy patients in an attempt to identify a possible defect in macrophage function. The ability of these cells to produce hydrogen peroxide and superoxide, two bactericidal metabolites of the monocyte/macrophage, has been measured. Monocytes from leprosy patients were found to be capable of producing normal amounts of hydrogen peroxide and superoxide, and no differences in production were found between tuberculoid, lepromatous and control monocytes. These results suggest that macrophages in leprosy are competent, and that probably a T lymphocyte defect contributes to susceptibility to this disease.

Susceptibility of Mycobacterium leprae to the bactericidal activity of mouse peritoneal macrophages and to hydrogen peroxide.

Macrophages from athymic nude mice were infected in vitro with Mycobacterium leprae to study the intracellular fate of this organism. Using the proportional bactericidal test, we have shown that the viability of M. leprae declines rapidly within these macrophages, although results of clearance experiments demonstrate that live and killed organisms are cleared at comparable rates. We have also shown that M. leprae is susceptible to the bactericidal effects of hydrogen peroxide and we suggest that hydrogen peroxide generated by macrophages is responsible for the killing of intracellular M. leprae.

Macrophage activity in Mycobacterium leprae infection.

The outcome of an M. leprae infection is likely to depend upon the balance between the invading organism and the host's immune response. Macrophages are known to play a major role in this response and because M. leprae is an intracellular parasite, being found commonly in the macrophages of infected hosts, we have attempted to examine the macrophage/M. leprae relationship. Our model has been the athymic nude mouse which has been shown to be susceptible to lepromatous infection but whose macrophages when cultured in vitro actually kill phagocytosed M. leprae. We have shown that in vitro this killing effect is probably mediated, at least to some extent, by macrophage-generated hydrogen peroxide. Further, we have examined macrophages from nude and normal mice at various stages of M. leprae infection in time of their ability to produce hydrogen peroxide and superoxide. It would appear from our results that activation of macrophages to produce these two bactericidal metabolites increases with increasing bacterial load. However, it would seem that T-cell mediated mechanisms are also required for effective control of infection as the hyperactive macrophages seen in the nude mouse are unable to control M. leprae growth in contrast to the limited infection seen in normal mice.

Attempts at cultivation of Mycobacterium leprae in macrophages from susceptible animal hosts.

Macrophages from nude mice, nude rats, and armadillos were cultured in vitro and examined for their ability to support Mycobacterium leprae. No significant growth of this organism were observed after over 200 days of culture. No significant benefit was derived from modifying culture conditions or from variations in the source of macrophages or the source of M. leprae.