Efferocytosis Is an Innate Antibacterial Mechanism

SummaryMycobacterium 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.

Graphical AbstractFigure optionsDownload high-quality image (239 K)Download as PowerPoint slideHighlights
► Apoptosis occurs after virulent Mycobacterium tuberculosis (Mtb) infection
► Mtb-infected dead cells are engulfed by uninfected macrophages via efferocytosis
► Efficient maturation of the bacteria-containing efferocytic phagosome kills Mtb
► Efferocytosis is an antibacterial effector mechanism both in vitro and in vivo