Mechanisms underlying the manipulation of host apoptotic pathways by Toxoplasma gondii.
The establishment of a productive infection by an obligate intracellular pathogen is dependent on subversion of cellular defences. Apoptosis, or programmed cell death, is a property of metazoan cells that plays a critical role in inhibiting the proliferation of invasive organisms and viruses thereby protecting uninfected cells and limiting damage to the host organism. Not surprisingly, manipulation of the machinery of apoptosis plays a critical role in the pathogenesis of several intracellular pathogens. Toxoplasma gondii, arguably one of the most successful protozoan pathogens, has evolved several strategies to inhibit both the initiation and propagation of the apoptotic cascade. Recent work from several groups indicates an exquisite level of sophistication in the mechanisms to inhibit apoptosis along its diverse pathways. Much of this ability appears to centre around the manipulation of host transcription, specifically of genes involved in the pro-survival/anti-apoptotic response effectively manipulating the infected cell into a highly anti-apoptotic state. The implications of these observations extend beyond Toxoplasma biology to the broader area of microbial pathogenesis and cell signalling in mammalian cells.