Mycobacteria and Macrophage Apoptosis: Complex Struggle for Survival M. avium-infected macrophages undergo apoptosis, but M. tuberculosis suppresses apoptosis and triggers necrosis

A lthough distinct, Mycobacterium tuberculosis and Mycobacterium avium both infect and survive in host macrophages. M. tuberculosis is more virulent, specifically adapted to humans, and grows poorly outside of the host. In contrast, M. avium can survive in the environment and also can infect several different host species in addition to humans, including birds, pigs, dogs, and monkeys. M. tuberculosis is primarily a pathogen of the respiratory tract, whereas M. avium, which can infect the lungs, can also gain access to hosts by crossing the intestinal barrier. Although M. avium infections in healthy individuals are rarely disseminated, this bacterium can persist within macrophages in mesenteric lymph nodes. Both types of bacteria survive within host mononuclear phagocytes, inhibiting vacuole acidification and phagosome-lysosome fusion. However, while the reactive nitrogen intermediates (RNIs) in activated macrophages kill M. tuberculosis, M. avium is resistant to RNIs. Following infection, virulent mycobacteria replicate within macrophages of susceptible hosts and subsequently infect surrounding macrophages. To spread the infection, mycobacteria escape one macrophage, probably once it becomes dysfunctional, to infect another. In the case of M. avium, infected macrophages undergo apoptosis, which triggers the escape of the bacterium, enabling it to spread to other cells. Meanwhile, M. tuberculosis inhibits apoptosis and exits cells by inducing necrosis. Apoptosis Amounts to an Innate Immune Response against M. tuberculosis