Macrophage apoptosis in mycobacterial infections

Abstract: Mycobacterial diseases are a major pub-lic health concern. In the case of tuberculosis, the problem has been acerbated due to the emergence of drug-resistant strains of Mycobacterium tubercu-losis, and Mycobacterium avium is the major oppor-tunistic pathogen in HIV-1 infection in the United States. M. tuberculosis and M. avium replicate in human macrophages and induce apoptosis. Incuba-tion of freshly added uninfected autologous macro-phages with apoptotic M. avium-infected macro-phages results in 90 % inhibition of bacterial growth. Apoptosis also prevents the release of intracellular components and the spread of mycobacterial infec-tion by sequestering the pathogens within apoptotic bodies. Consistent with the model that host cell apoptosis is a defense mechanism against mycobac-teria is the finding that the virulent M. tuberculosis strain H37Rv induces substantially less macro-phage apoptosis than the attenuated strain H37Ra. Evasion of apoptosis by this pathogen is achieved by enhanced release of sTNFR2 by H37Rv-infected macrophages and subsequent formation of inactive TNF-a-TNFR2 complexes. These observations con-tribute to the hypothesis that apoptosis of the host macrophage is an important defense mechanism in mycobacterial infections, which prevents the spread of the infection. J. Leukoc. Biol. 66: 763–764; 1999. Key Words: Mycobacterium tuberculosis · Mycobacterium avium · tumor necrosis factor · HIV-