22980326

PMC3517204

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.

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5P30AI060354/AI/NIAID NIH HHS/United States
DP2-0D001378/DP/NCCDPHP CDC HHS/United States
P30 AI060354/AI/NIAID NIH HHS/United States
R01 AI098637/AI/NIAID NIH HHS/United States
R01AI072143/AI/NIAID NIH HHS/United States
R56AI084161/AI/NIAID NIH HHS/United States
T32 AI007387/AI/NIAID NIH HHS/United States
T32-AI07387/AI/NIAID NIH HHS/United States
TL1 RR029881/RR/NCRR NIH HHS/United States
UL1 RR029882/RR/NCRR NIH HHS/United States