Macrophage apoptosis in mycobacterial infections

Mycobacterial diseases are a major public health concern. In the case of tu berculosis, the problem has been acerbated due to the emergence of drug-res istant strains of Mycobacterium tuberculosis, and Mycobacterium avium is th e major opportunistic pathogen in HIV-1 infection in the United States, M. tuberculosis and M. avium replicate in human macrophages and induce apoptos is, Incubation of freshly added uninfected autologous macrophages with apop totic M. avium-infected macrophages results in 90% inhibition of bacterial growth. Apoptosis also prevents the release of intracellular components and the spread of mycobacterial infection by sequestering the pathogens within apoptotic bodies. Consistent with the model that host cell apoptosis is a defense mechanism against mycobacteria is the finding that the virulent ill . tuberculosis strain H37Rv induces substantially less macrophage apoptosis than the attenuated strain H37Ra, Evasion of apoptosis by this pathogen is achieved by enhanced release of sTNFR2 by H57Rv-infected macrophages and s ubsequent formation of inactive TNF-alpha-TNFR2 complexes. These observatio ns contribute to the hypothesis that apoptosis of the host macrophage is an important defense mechanism in mycobacterial infections, which prevents th e spread of the infection.