Evasion of innate immunity by Mycobacterium tuberculosis: is death an exit strategy?

In this Opinion article, the authors describe howMycobacterium tuberculosisinfection of host macrophages affects the balance of host lipid mediators and, in doing so, alters the plasma membrane repair and mitochondrial-damage pathways. As a consequence, bacterial virulence influences whether macrophage death occurs by apoptosis or necrosis. Virulent Mycobacterium tuberculosis inhibits apoptosis and triggers necrosis of host macrophages to evade innate immunity and delay the initiation of adaptive immunity. By contrast, attenuated M. tuberculosis induces macrophage apoptosis, an innate defence mechanism that reduces bacterial viability. In this Opinion article, we describe how virulent M. tuberculosis blocks production of the eicosanoid lipid mediator prostaglandin E2 (PGE2). PGE2 production by infected macrophages prevents mitochondrial damage and initiates plasma membrane repair, two processes that are crucial for preventing necrosis and inducing apoptosis. Thus, M. tuberculosis-mediated modulation of eicosanoid production determines the death modality of the infected macrophage, which in turn has a substantial impact on the outcome of infection.