"With a little help from my friends": efferocytosis as an antimicrobial mechanism

Abstract

The uptake of apoptotic cells by phagocytes is defined as efferocytosis. In this issue of Cell Host & Microbe, Martin et al. (2012) and Yang et al. (2012) report that macrophage- and neutrophil-mediated efferocytosis of apoptotic cells containing mycobacteria is an innate antibacterial effector mechanism.

Figure 1. Efferocytosis is an innate host defense mechanism

The genotype of host cell and mycobacterium both determine if infection induces either necrotic or apoptotic cells death. For example, virulent Mtb strains are able to increase lipoxin A₄ (LXA₄) and decrease prostaglandin E₂ (PGE₂) levels, whereas the inverse is true for attenuated strains of Mtb. Apoptotic macrophages can be ingested by uninfected macrophages or neutrophils in a process defined as efferocytosis. The Mtbphagosome generated during efferocytosis is enriched in lysosomal markers, recruits the vacular ATPase and becomes acidic. This process is defined as phagosome maturation and leads to killing of bacteria combined with the increase in reactive oxygens species generated by the host cell NOX2 complex. In contrast, necrosis of host macrophages releases bacteria which can then infect other phagocytes, inhibit phagosome maturation, replicate and induce host cell necrosis to repeat the cycle.