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.