J Keane1, B Shurtleff, H Kornfeld. 1. Pulmonary Center, Boston University School of Medicine, Boston, MA, USA. jkeane@lung.bumc.bu.edu
Abstract
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.
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 -infectedmurine 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.
Authors: Philana Ling Lin; Amy Myers; Le'Kneitah Smith; Carolyn Bigbee; Matthew Bigbee; Carl Fuhrman; Heather Grieser; Ion Chiosea; Nikolai N Voitenek; Saverio V Capuano; Edwin Klein; JoAnne L Flynn Journal: Arthritis Rheum Date: 2010-02
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Authors: Mohammad Fallahi-Sichani; Matthew A Schaller; Denise E Kirschner; Steven L Kunkel; Jennifer J Linderman Journal: PLoS Comput Biol Date: 2010-05-06 Impact factor: 4.475