Listeria monocytogenes exploits efferocytosis to promote cell-to-cell spread

The intracellular bacterial pathogen Listeria monocytogenes is shown to exploit efferocytosis—the process by which dead or dying cells are removed by phagocytosis—to promote cell-to-cell spread during infection. Phagocytosis coopted by bacterial pathogens This study of the intracellular bacterial pathogen Listeria monocytogenes , a significant cause of foodborne illness, shows that it exploits the host's efferocytosis system to promote cell-to-cell spread during infection. Efferocytosis is the process by which dead or dying cells are removed by phagocytosis and it relies in part on the receptors that bind to exofacial phosphatidylserine on the surface of cells or cellular debris following the loss of plasma membrane asymmetry. Listerial actin-based motility leads to the formation of protrusions at the cell surface of infected cells, eventually leading to uptake of bacteria by adjacent cells. These findings identify phosphatidylserine as a possible drug target in infections by L. monocytogenes and other bacteria using similar strategies of cell-to-cell spread during infection. Efferocytosis, the process by which dying or dead cells are removed by phagocytosis, has an important role in development, tissue homeostasis and innate immunity 1 . Efferocytosis is mediated, in part, by receptors that bind to exofacial phosphatidylserine (PS) on cells or cellular debris after loss of plasma membrane asymmetry. Here we show that a bacterial pathogen, Listeria monocytogenes , can exploit efferocytosis to promote cell-to-cell spread during infection. These bacteria can escape the phagosome in host cells by using the pore-forming toxin listeriolysin O (LLO) and two phospholipase C enzymes 2 . Expression of the cell surface protein ActA allows L. monocytogenes to activate host actin regulatory factors and undergo actin-based motility in the cytosol, eventually leading to formation of actin-rich protrusions at the cell surface. Here we show that protrusion formation is associated with plasma membrane damage due to LLO’s pore-forming activity. LLO also promotes the release of bacteria-containing protrusions from the host cell, generating membrane-derived vesicles with exofacial PS. The PS-binding receptor TIM-4 (encoded by the Timd4 gene) contributes to efficient cell-to-cell spread by L. monocytogenes in macrophages in vitro and growth of these bacteria is impaired in Timd4 −/− mice. Thus, L. monocytogenes promotes its dissemination in a host by exploiting efferocytosis.