Mechanisms of Toxicity of Tubercle Bacilli for Macrophages

The early studies of Lurie1 clearly established that virulent tubercle bacilli are highly infectious for susceptible hosts. For example, he observed repeatedly that one colony-forming unit (CFU) of the highly virulent H37Rv strain of Mycobacterium tuberculosis could develop one tubercle in the lungs of susceptible rabbits. Although not proved at that time, it is likely that even one organism is capable of producing one tubercle in the lungs of NZW rabbits (noninbred). By contrast, the H37Ra strain, an avirulent mutant of the H37Rv strain, is incapable of replicating in the macrophages of normal rabbits. Lurie’s findings were particularly important with respect to the multiplication of the attenuated BCG strain of Mycobacterium bovis. In this case, even though BCG could not produce progressive infection in the rabbit, it was able to multiply in normal alveolar macrophages (AM) essentially at the same rate as the virulent H37Rv strain prior to the time specific cell-mediated immunity was acquired. All these early studies indicated that normal AM are incapable of inhibiting or containing the multiplication of phagocytosed organisms of the virulent H37Rv strain of M. tuberculosis, as well as the attenuated BCG strain during the early intervals after infection. Accordingly, Lurie concluded that all the immunity expressed against M. tuberculosis is acquired after infection. Lurie also demonstrated that macrophages from immune animals were resistant to the replication of virulent mycobacteria. These observations suggested that pathogenic mycobacteria have some virulence mechanism that enables them to multiply in normal macrophages, whereas immunologically activated macrophages are capable of inhibiting the growth of virulent mycobacteria.