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

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

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Title: Listeria monocytogenes exploits efferocytosis to promote cell-to-cell spread
Author: Czuczman, Mark A.; Fattouh, Ramzi; van Rijn, Jorik; Canadien, Veronica; Osborne, Suzanne; Muise, Aleixo M.; Kuchroo, Vijay K.; Higgins, Darren E.; Brumell, John H.

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Citation: Czuczman, Mark A., Ramzi Fattouh, Jorik van Rijn, Veronica Canadien, Suzanne Osborne, Aleixo M. Muise, Vijay K. Kuchroo, Darren E. Higgins, and John H. Brumell. 2014. “Listeria monocytogenes exploits efferocytosis to promote cell-to-cell spread.” Nature 509 (7499): 230-234. doi:10.1038/nature13168.
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Abstract: Efferocytosis, the process by which dying/dead cells are removed by phagocytosis, plays an important role in development, tissue homeostasis and innate immunity1. 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 (Lm), can exploit efferocytosis to promote cell-to-cell spread during infection. These bacteria can escape the phagosome in host cells using the pore-forming toxin Listeriolysin O (LLO) and two phospholipases C2. Expression of the cell surface protein ActA allows Lm 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. 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 contributes to efficient cell-to-cell spread by Lm in macrophages in vitro and growth of these bacteria is impaired in TIM-4−/− mice. Thus, Lm promotes its dissemination in a host by exploiting efferocytosis. Our study suggests that PS-targeted therapeutics may be useful in the fight against infections by Lm and other bacteria that utilize similar strategies of cell-to-cell spread during infection.
Published Version: doi:10.1038/nature13168
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