Infect Immun. 2008 Aug 4. [Epub ahead of print]
Toxoplasma gondii Rhoptry Discharge Correlates with Activation of the EGR2 Host Cell Transcription Factor
Phelps ED, Sweeney KR, Blader IJ.
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
Toxoplasma gondii is a ubiquitous Apicomplexan parasite that can cause severe disease in fetuses and immune-compromised patients. Rhoptries, micronemes, and dense granules, which are secretory organelles unique to Toxoplasma and other Apicomplexan parasites, play critical roles in parasite growth and virulence. To understand how these organelles modulate infected host cells, we sought to identify host cell transcription factors triggered by their release. EGR2 is a host cell transcription factor that is rapidly upregulated and activated in Toxoplasma-infected cells but not in cells infected with the closely related Apicomplexan parasite Neospora caninum. EGR2 upregulation only occurred when live parasites were in direct contact with the host cell and not by cell extracts that contain dense granule or micronemal proteins. When microneme-mediated attachment was blocked by pre-treating parasites with a calcium chelator, EGR2 expression was significantly reduced. In contrast, when host cells were infected with parasites in the presence of cytochalasin D, which allows rhoptry secretion but prevents parasite invasion, EGR2 was activated. Finally, we demonstrate that Toxoplasma activation of host p38 MAP kinase is necessary but not sufficient for EGR2 activation. Collectively, these data indicate that EGR2 is specifically upregulated by a parasite-derived secreted factor that is most likely a resident rhoptry protein.
PMID: 18678671 [PubMed - as supplied by publisher]