QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 9 September 2003
doi: 10.1242/jcs.00683

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.00683v1 116/21/4359    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Molestina, R. E. Articles by Sinai, A. P. Search for Related Content PubMed PubMed Citation Articles by Molestina, R. E. Articles by Sinai, A. P. Social Bookmarking                         What's this?

Activation of NF-B by Toxoplasma gondii correlates with increased expression of antiapoptotic genes and localization of phosphorylated IB to the parasitophorous vacuole membrane

¹ Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536, USA
² Infectious Diseases Section, Yale University School of Medicine, New Haven, CT 06520, USA

^* Author for correspondence (e-mail: sinai{at}uky.edu.)

Accepted 27 May 2003

Mammalian cells infected with Toxoplasma gondii are resistant to apoptosis induced by a variety of stimuli. We have demonstrated that the host transcription factor NF-B plays a pivotal role in the T.-gondii-mediated blockade of apoptosis because inhibition is lost in cells lacking the p65 (RelA) subunit of NF-B (p65^–/–). In the present study, we examined the effects of T. gondii infection on NF-B activation and the expression of genes involved in the apoptotic cascade. Infection of wild-type mouse embryonic fibroblasts (MEFs) with T.-gondii-induced nuclear translocation of the p50 and p65 subunits of NF-B as examined by immunoblotting of nuclear extracts, immunofluorescence and electrophoretic mobility shift assays. A comparison of apoptotic gene expression profiles from wild-type and p65^–/– MEFs revealed distinct patterns of induction in response to T. gondii infection. In particular, the differences seen in the Bcl-2 and IAP families are consistent with the antiapoptotic responses observed in the resistant wild-type cells compared with the sensitive p65^–/– fibroblasts. Consistent with NF-B activation, T. gondii infection promoted phosphorylation of the inhibitor IB. Interestingly, phosphorylated IB was concentrated on the parasitophorous vacuole membrane (PVM), suggesting a parasite-directed event. Results from this study suggest that activation of NF-B plays an important role in stimulation of antiapoptotic gene expression by T. gondii. Furthermore, recruitment of phosphorylated IB to the PVM implies the presence of intrinsic factor(s) in T. gondii that might be used to manipulate the NF-B signaling pathway in the host to elicit a survival response during infection.

Key words: Toxoplasma gondii, Apoptosis, NF-B, IB, Bcl2, IAP

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in JCS:

Death-defying Toxoplasma

JCS 2003 116: 2104. [Full Text]  

This article has been cited by other articles:

				C.-H. Ju, A. Chockalingam, and C. A. Leifer Early Response of Mucosal Epithelial Cells during Toxoplasma gondii Infection J. Immunol., December 1, 2009; 183(11): 7420 - 7427. [Abstract] [Full Text] [PDF]

				D. Hippe, A. Weber, L. Zhou, D. C. Chang, G. Hacker, and C. G. K. Luder Toxoplasma gondii infection confers resistance against BimS-induced apoptosis by preventing the activation and mitochondrial targeting of pro-apoptotic Bax J. Cell Sci., October 1, 2009; 122(19): 3511 - 3521. [Abstract] [Full Text] [PDF]

				E. D. Phelps, K. R. Sweeney, and I. J. Blader Toxoplasma gondii Rhoptry Discharge Correlates with Activation of the Early Growth Response 2 Host Cell Transcription Factor Infect. Immun., October 1, 2008; 76(10): 4703 - 4712. [Abstract] [Full Text] [PDF]

				D. Hippe, O. Lytovchenko, I. Schmitz, and C. G. K. Luder Fas/CD95-Mediated Apoptosis of Type II Cells Is Blocked by Toxoplasma gondii Primarily via Interference with the Mitochondrial Amplification Loop Infect. Immun., July 1, 2008; 76(7): 2905 - 2912. [Abstract] [Full Text] [PDF]

				M. M. Nelson, A. R. Jones, J. C. Carmen, A. P. Sinai, R. Burchmore, and J. M. Wastling Modulation of the Host Cell Proteome by the Intracellular Apicomplexan Parasite Toxoplasma gondii Infect. Immun., February 1, 2008; 76(2): 828 - 844. [Abstract] [Full Text] [PDF]

				E. K. Persson, A. M. Agnarson, H. Lambert, N. Hitziger, H. Yagita, B. J. Chambers, A. Barragan, and A. Grandien Death Receptor Ligation or Exposure to Perforin Trigger Rapid Egress of the Intracellular Parasite Toxoplasma gondii J. Immunol., December 15, 2007; 179(12): 8357 - 8365. [Abstract] [Full Text] [PDF]

				R. K. Herman, R. E. Molestina, A. P. Sinai, and D. K. Howe The Apicomplexan Pathogen Neospora caninum Inhibits Host Cell Apoptosis in the Absence of Discernible NF-{kappa}B Activation Infect. Immun., September 1, 2007; 75(9): 4255 - 4262. [Abstract] [Full Text] [PDF]

				M. E. Lasbury, S. Merali, P. J. Durant, D. Tschang, C. A. Ray, and C.-H. Lee Polyamine-mediated Apoptosis of Alveolar Macrophages during Pneumocystis Pneumonia J. Biol. Chem., April 13, 2007; 282(15): 11009 - 11020. [Abstract] [Full Text] [PDF]

				V. P. Losick and R. R. Isberg NF-{kappa}B translocation prevents host cell death after low-dose challenge by Legionella pneumophila J. Exp. Med., September 4, 2006; 203(9): 2177 - 2189. [Abstract] [Full Text] [PDF]

				M. Okomo-Adhiambo, C. Beattie, and A. Rink cDNA Microarray Analysis of Host-Pathogen Interactions in a Porcine In Vitro Model for Toxoplasma gondii Infection Infect. Immun., July 1, 2006; 74(7): 4254 - 4265. [Abstract] [Full Text] [PDF]

				L. Kim and E. Y. Denkers Toxoplasma gondii triggers Gi-dependent PI 3-kinase signaling required for inhibition of host cell apoptosis J. Cell Sci., May 15, 2006; 119(10): 2119 - 2126. [Abstract] [Full Text] [PDF]

				R. E. Molestina and A. P. Sinai Host and parasite-derived IKK activities direct distinct temporal phases of NF-{kappa}B activation and target gene expression following Toxoplasma gondii infection J. Cell Sci., December 15, 2005; 118(24): 5785 - 5796. [Abstract] [Full Text] [PDF]

				B. Sukumaran, J. A. Carlyon, J.-L. Cai, N. Berliner, and E. Fikrig Early Transcriptional Response of Human Neutrophils to Anaplasma phagocytophilum Infection Infect. Immun., December 1, 2005; 73(12): 8089 - 8099. [Abstract] [Full Text] [PDF]

				S. Shapira, O. S. Harb, J. Margarit, M. Matrajt, J. Han, A. Hoffmann, B. Freedman, M. J. May, D. S. Roos, and C. A. Hunter Initiation and termination of NF-{kappa}B signaling by the intracellular protozoan parasite Toxoplasma gondii J. Cell Sci., August 1, 2005; 118(15): 3501 - 3508. [Abstract] [Full Text] [PDF]

				S. Das, J. Cho, I. Lambertz, M. A. Kelliher, A. G. Eliopoulos, K. Du, and P. N. Tsichlis Tpl2/Cot Signals Activate ERK, JNK, and NF-{kappa}B in a Cell-type and Stimulus-specific Manner J. Biol. Chem., June 24, 2005; 280(25): 23748 - 23757. [Abstract] [Full Text] [PDF]

				T. M. Payne, R. E. Molestina, and A. P. Sinai Inhibition of caspase activation and a requirement for NF-{kappa}B function in the Toxoplasma gondii-mediated blockade of host apoptosis J. Cell Sci., November 1, 2003; 116(21): 4345 - 4358. [Abstract] [Full Text] [PDF]