Paracytophagy

The process of paracytophagy[1] was first described as a crucial step during cell-to-cell spread of the intracellular bacterial pathogen Listeria monocytogenes, and is also commonly observed in Shigella flexneri.

The polymerization of actin filaments is responsible for the formation of pseudopods, filopodia and lamellipodia during cell motility.

Studies of these bacteria, especially of Listeria Actin assembly-inducing protein (ActA), have resulted in further understanding of the actions of WASP.

[5] A distinct process known as trogocytosis, the exchange of lipid rafts or membrane patches between immune cells, can facilitate response to foreign stimuli.

[4] The two main examples of paracytophagy are the modes of cell-cell transmission of Listeria monocytogenes and Shigella flexneri.

[1] The following is a description of the process of cell-cell transmission of Listeria monocytogenes, primarily based on Robbins et al. (1999):[1] In an already infected "donor" cell, the Listeria bacterium expresses ActA, which results in formation of the actin comet tail and movement of the bacterium throughout the cytoplasm.

The close interaction between the bacterium and the host cell membrane is thought to depend on Ezrin, a member of the ERM family of membrane-associated proteins.

At this point, the bacterium at the tip of the protrusion will begin to undergo "fitful movement" caused by continuing polymerization of actin at its rear.

Within 5 minutes, the target cell becomes infected when the secondary vacuole begins to acidify and the inner (donor cell-derived) membrane breaks down through the action of bacterial phospholipases (PI-PLC and PC-PLC).

Using these phagocytic cells as vectors, Listeria travels throughout the nerves and reaches tissues usually inaccessible to other bacterial pathogens.

Listeria uses phagocytic leukocytes as a “Trojan Horse” [18] to gain access to a greater range of target cells.

In one study, mice treated with gentamicin via infusion pump displayed CNS and brain involvement during infection with Listeria, indicating that the population of bacteria responsible for severe pathogenesis resided within cells and was protected from the circulating antibiotic.

Bacteria have not been shown to infect neuronal cells directly in an efficient manner, and the previously described macrophage hand-off is thought to be necessary for this mode of spread.