Following infection, the intracellular protozoan parasite Toxoplasma gondii (T. gondii) induces morphological and biochemical changes to its host cell. Previous studies have reported changes in the levels of several pro-inflammatory cytokines, redistribution of host cell organelles, and protection of the host cell from undergoing apoptosis. To examine the basis of these and other changes, gene expression profiles of human foreskin fibroblasts infected with T. gondii were studied using cDNA microarrays. The microarrays used were spotted with approximately 22,000 sequence-verified known genes and uncharacterized ESTs. RNA isolated from infected host cells was compared to mock-infected cells. Early during infection (1-2 h), the majority of transcripts induced, encode proteins associated with the pro-inflammatory response. These genes are also induced by secreted, soluble factors from extracellular parasites indicating this early host response does not require parasite invasion. Later during infection, a large number of additional genes are modulated which are involved in numerous cellular processes including the glycolytic, cholesterol and nucleoside metabolic pathways. Many genes in this latter class are dependent on the direct presence of the parasite as opposed to secreted products derived from either the parasite or infected cells. The results reveal many previously unknown effects on the host cell and lay the foundation for detailed analysis of the underlying molecular mechanisms.
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