Transitory macrophage activation in the granulomatous lesions of Mycobacterium lepraemurium-induced lepromatoid leprosy in the mouse.

A kinetic study on the evolution of granulomas that appear in the liver of NIH mice inoculated with 10(8) Mycobacterium lepraemurium by the intraperitoneal route has been performed. The liver was chosen because of its nonlymphoid histology which allowed us to visualize the appearance and maturation of the cell infiltrates generated as a consequence of the mycobacterial infection. The study analyzed both the macrophage activation within the granulomas and the fate of bacilli within the macrophage. The results showed that this mycobacteriosis induces a relatively early macrophage activation (a very likely result of a cell-mediated immune response triggered by the bacilli) that peaks between 45 and 60 days postinoculation, fades thereafter, and practically disappears several days later. Bacilli are susceptible to the microbicidal effects of activated macrophages, but when the macrophages are turned off (probably due to active suppressive mechanisms), the surviving bacilli reinitiate the infection with no further macrophage opposition. As a result, more phagocytes are attracted to the infection sites and the cell infiltrates grow steadily to become confluent, increasing the granuloma fraction and eventually replacing the liver parenchyma. The findings suggest that in murine "leprosy" infection, early immunological changes occur that enable the macrophages present in the granulomas to kill the infecting M. lepraemurium regardless of the eventual lepromatoid evolution of the granulomas. Lepromatoid granulomas in the mouse and lepromatous granulomas in man are equivalent structures in regard to their histology and bacteriology.