Escape of Mycobacterium tuberculosis from oxidative killing by neutrophils

: Neutrophils enter sites of infection, where they can eliminate pathogenic bacteria in an oxidative manner. Despite their predominance in active tuberculosis lesions, the function of neutrophils in this important human infection is still highly controversial. We observed that virulent M. tuberculosis survived inside human neutrophils despite prompt activation of these defence cell's microbicidal effectors by mycobacterial infection. Survival of M. tuberculosis was accompanied by necrotic cell death of infected neutrophils. Necrotic cell death entirely depended on radical oxygen species (ROS) production since chronic granulomatous disease (CGD) neutrophils were protected from M. tuberculosis-triggered necrosis. More, importantly, the M. tuberculosis?RD1 mutant failed to induce neutrophil necrosis rendering this strain susceptible to ROS-mediated killing. We conclude that this virulence function is instrumental for M. tuberculosis to escape killing by neutrophils and contributes to pathogenesis in tuberculosis. © 2012 Blackwell Publishing Ltd.