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Originally published In Press as doi:10.1074/jbc.M100951200 on April 9, 2001

J. Biol. Chem., Vol. 276, Issue 26, 24223-24231, June 29, 2001
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Microarray Analysis Reveals Previously Unknown Changes in Toxoplasma gondii-infected Human Cells*

Ira J. BladerDagger , Ian D. Manger§, and John C. Boothroyd

From the Department of Microbiology and Immunology, Stanford University, Stanford, California 94305-5124

Cells infected with the intracellular protozoan parasite Toxoplasma gondii undergo up-regulation of pro-inflammatory cytokines, organelle redistribution, and protection from apoptosis. To examine the molecular basis of these and other changes, gene expression profiles of human foreskin fibroblasts infected with Toxoplasma were studied using human cDNA microarrays consisting of ~22,000 known genes and uncharacterized expressed sequence tags. Early during infection (1-2 h), <1% of all genes show a significant change in the abundance of their transcripts. Of the 63 known genes in this group, 27 encode proteins associated with the immune response. These genes are also up-regulated by secreted, soluble factors from extracellular parasites indicating that the early response does not require parasite invasion. Later during infection, genes involved in numerous host cell processes, including glucose and mevalonate metabolism, are modulated. Many of these late genes are dependent on the direct presence of the parasite; i.e. secreted products from either the parasite or infected cells are insufficient to induce these changes. These results reveal several previously unknown effects on the host cell and lay the foundation for detailed analysis of their role in the host-pathogen interaction.


* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Supported by National Institutes of Health Grant 1F32AI10478-01.

§ Current address: Mycometrix, 213 E. Grand Ave., South San Francisco, CA 94080.

Supported by National Institutes of Health Grants AI21423 and AI45057. To whom correspondence should be addressed: Dept. of Microbiology and Immunology, Stanford University, 299 Campus Dr., Stanford, CA 94305-5124. Tel.: 650-723-7984; Fax: 650-723-6853; E-mail: john.boothroyd@Stanford.edu.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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