TNF-dependent BALB/c murine macrophage apoptosis following Mycobacterium tuberculosis infection inhibits bacillary growth in an IFN-γ independent manner

Setting: In vitro model of murine macrophage M. tuberculosis infection. Objective: To evaluate the association and cytokine control of host cell apoptosis and bacillary killing in M. tuberculosis-infected murine peritoneal macrophage (PM). Design: Murine PM from different strains of mice were infected with H37Ra. Bacillary growth and macrophage apoptosis were evaluated under different cytokine conditions. Results: Like human alveolar macrophages, PM from BALB/c mice were found to undergo apoptosis after infection with M. tuberculosis in a TNF-dependent manner. Neutralizing TNF with anti-TNF antibody inhibited PM apoptosis following infection, and resulted in increased bacillary growth. Pre-treatment of PM with interferon (IFN-gamma) resulted in significant killing of the infecting bacilli, which was not dependent on TNF or apoptosis of the cells. In contrast to BALB/c mice, PM from C3H/HeJ mice did not undergo apoptosis following infection and did not undergo TNF- and apoptosis-dependent inhibition of bacillary growth. Conclusion: These findings suggest that TNF contributes to macrophage inhibition of M. tuberculosis growth by a mechanism that is dependent on apoptosis and independent of IFN-gamma activity. This protective phenotype was not seen in all strains of mice and merits investigation as a marker of mycobacterial host susceptibility. (C) 2002 Elsevier Science Ltd. All rights reserved.