FEATURE ARTICLE
Pathogens, Host-Cell Invasion and Disease
Invading pathogens can co-opt even the cells of the immune system. New anti-infective drugs may arise from an understanding of this chemical warfare
Erich Gulbins, Florian Lang
Assisted Apoptosis
A few pathogens use a rather sophisticated approach to kill the infected cell: They trigger it to commit suicide. This process, called apoptosis, is not a sudden burst of the cell, but rather a controlled shutdown of the cell's biochemical machinery and disassembly of its constituents.
Apoptosis is not unique to infected cells, but is a normal process that can be triggered by a variety of stimuli, such as radiation or the stimulation of proteins on the cell's surface, such as the CD95 or the P2X7 receptors. Caspases, a family of enzymes that are specialized in cleaving proteins, play a key role in apoptosis. Once activated, caspases trigger further events in the cell that break down the DNA in the nucleus, switch off and disintegrate the mitochondria (the energy-producing cell organelles) and lead to a rearrangement of the surrounding plasma membrane. This chain of events finally causes the cell to shrink and decompose into smaller particles that are taken up and digested by macrophages in the vicinity.
Shigella triggers apoptosis of the infected macrophage in order to gain access to the underlying tissue, from which it can spread to other cells. Also, the ability to drive macrophages to cell death can protect a pathogen from being killed by those cells. Yersinia, for example, induces apoptosis as a way to escape from a macrophage before being digested. In fact, Yersinia bacteria that are unable to trigger apoptosis because of a defective YopJ protein are unable to kill macrophages and are thus less virulent than Yersinia with an intact YopJ protein.
Bacteria may trigger apoptosis by injecting proteins via their type III secretion system into the target cell. For instance, some of the proteins that Shigella and Salmonella inject through the type III secretory system stimulate the host cell's caspase I proteins. Yersinia, the plague-causing bacterium, injects a protein called YopJ into the target cell to trigger its internalization. YopJ also inhibits certain signaling proteins in the host cell, which usually suppress apoptosis. The release of YopJ by the bacterium thus triggers suicide of the infected cell.
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