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


METHODS
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.


CONCLUSIONS
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.
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000382:microbiology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development*; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma