Infection by Toxoplasma gondii Specifically Induces Host c-Myc and the Genes This Pivotal Transcription Factor Regulates

Toxoplasma gondii infection has previously been described to cause dramatic changes in the host transcriptome by manipulating key regulators, including STATs, NF-κB, and microRNAs. Here, we report thatToxoplasma tachyzoites also mediate rapid and sustained induction of another pivotal regulator of host cell transcription, c-Myc. This induction is seen in cells infected with all three canonical types ofToxoplasma but not the closely related apicomplexan parasiteNeospora caninum . Coinfection of cells with bothToxoplasma andNeospora still results in an increase in the level of host c-Myc, showing that c-Myc is actively upregulated byToxoplasma infection (rather than repressed byNeospora ). We further demonstrate that this upregulation may be mediated through c-Jun N-terminal protein kinase (JNK) and is unlikely to be a nonspecific host response, as heat-killedToxoplasma parasites do not induce this increase and neither do nonviable parasites inside the host cell. Finally, we show that the induced c-Myc is active and that transcripts dependent on its function are upregulated, as predicted. Hence, c-Myc represents an additional way in whichToxoplasma tachyzoites have evolved to specifically alter host cell functions during intracellular growth.