KILLING OF MYCOBACTERIUM-SMEGMATIS BY MACROPHAGES FROM GENETICALLY SUSCEPTIBLE AND RESISTANT MICE

The bactericidal function of macrophages was investigated in congenic mice expressing the phenotype of susceptibility (B10.A,Bcg(s)) or resistance (B10.A.Bcg(r)) to mycobacterial infection. When splenic and peritoneal macrophages from these two mouse strains were infected in vitro with Mycobacterium smegmatis, the Bcg(r) macrophages were shown to inactivate M. smegmatis more efficiently than their Bcg(s) congenic counterparts. The mechanisms of this superior antimycobacterial activity was studied further. Addition of catalase did not abolish killing to a significant degree in either allelic type of macrophage, suggesting that hydrogen peroxide production was not involved in the killing activity controlled by the Bcg gene. Activation of Bcg(s) macrophages by exposure to crude lymphokines rendered them equally as efficient as their Bcg(r) counterparts in their capacity to destroy M. smegmatis. This finding suggests that both the genetically resistant and susceptibile macrophages have the potential to kill M. smegmatis in vitro. This potential is expressed constitutively by the Bcg(r) but not Bcg(s) macrophages and can be induced, by lymphokine treatment, in the Bcg(s) macrophages, In a final set of experiments, the macrophage killing of M. smegmatis was evaluated as a test system to type for the Bcg gene allelic type in vitro, using a set of AXB and BXA recombinant inbred strains of mice. Results obtained show that typing of AXB/BXA recombinant inbred strains for the trait of bactericidal activity vs. M. smegmatis in vitro revealed a perfect match with the strain distribution pattern of resistance/susceptibility to Mycobacterium bovis BCG in vivo.