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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
Microarray Analysis Reveals Previously Unknown
Changes in Toxoplasma gondii-infected Human Cells*
Ira J.
Blader ,
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.
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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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
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