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Infection and Immunity, October 2008, p. 4703-4712, Vol. 76, No. 10
0019-9567/08/$08.00+0     doi:10.1128/IAI.01447-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Toxoplasma gondii Rhoptry Discharge Correlates with Activation of the Early Growth Response 2 Host Cell Transcription Factor {triangledown}

Eric D. Phelps, Kristin R. Sweeney, and Ira J. Blader*

Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104

Received 29 October 2007/ Returned for modification 20 November 2007/ Accepted 13 July 2008

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. Early growth response 2 (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 occurred only when live parasites were in direct contact with the host cell and not from exposure to cell extracts that contain dense granule or micronemal proteins. When microneme-mediated attachment was blocked by pretreating 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 mitogen-activated protein 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.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, BMSB 1034, 940 Stanton L. Young Blvd., Oklahoma City, OK 73104. Phone: (405) 271-2133. Fax: (405) 271-3117. E-mail: iblader{at}ouhsc.edu

{triangledown} Published ahead of print on 4 August 2008.

Editor: J. F. Urban, Jr.


Infection and Immunity, October 2008, p. 4703-4712, Vol. 76, No. 10
0019-9567/08/$08.00+0     doi:10.1128/IAI.01447-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.