Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Cell Host Microbe. 2012 Sep 13;12(3):289-300. doi: 10.1016/j.chom.2012.06.010.
Mycobacterium tuberculosis persists within macrophages in an arrested phagosome and depends upon necrosis to elude immunity and disseminate. Although apoptosis of M. tuberculosis-infected macrophages is associated with reduced bacterial growth, the bacteria are relatively resistant to other forms of death, leaving the mechanism underlying this observation unresolved. We find that after apoptosis, M. tuberculosis-infected macrophages are rapidly taken up by uninfected macrophages through efferocytosis, a dedicated apoptotic cell engulfment process. Efferocytosis of M. tuberculosis sequestered within an apoptotic macrophage further compartmentalizes the bacterium and delivers it along with the apoptotic cell debris to the lysosomal compartment. M. tuberculosis is killed only after efferocytosis, indicating that apoptosis itself is not intrinsically bactericidal but requires subsequent phagocytic uptake and lysosomal fusion of the apoptotic body harboring the bacterium. While efferocytosis is recognized as a constitutive housekeeping function of macrophages, these data indicate that it can also function as an antimicrobial effector mechanism.
结核分枝杆菌在被吞噬的吞噬体中处于静止状态而得以在巨噬细胞内存活，并依赖于坏死来逃避免疫和传播。虽然感染结核分枝杆菌的巨噬细胞凋亡与细菌生长减少有关，但细菌对其他形式的死亡相对具有抗性，这使得这种观察结果的机制仍未得到解决。我们发现，在凋亡之后，感染结核分枝杆菌的巨噬细胞通过吞噬作用（一种专门的凋亡细胞吞噬过程）被未感染的巨噬细胞迅速摄取。吞噬作用将被吞噬在凋亡巨噬细胞内的结核分枝杆菌进一步分隔，并将其与凋亡细胞碎片一起运送到溶酶体室。只有在吞噬作用之后，结核分枝杆菌才会被杀死，这表明凋亡本身并不具有内在的杀菌作用，但需要随后吞噬被感染的凋亡细胞并使溶酶体融合。尽管吞噬作用被认为是巨噬细胞的固有细胞稳态功能，但这些数据表明，它也可以作为一种抗微生物效应机制。
