Microarray analysis reveals previously unknown changes in Toxoplasma gondii-infected human cells

Cells infected with the intracellular protozoan parasite Toxoplasma gondii undergo up-regulation of proinflammatory cytokines, organelle redistributio n, and protection from apoptosis, To examine the molecular basis of these a nd other changes, gene expression pro files of human foreskin fibroblasts i nfected with Toxoplasma were studied using human cDNA microarrays consistin g of similar to 22,000 known genes and uncharacterized expressed sequence t ags. Early during infection (1-2 h), <1% of all genes show a significant ch ange in the abundance of their transcripts. Of the 63 known genes in this g roup, 27 encode proteins associated with the immune response. These genes a re also up-regulated by secreted, soluble factors from extracellular parasi tes indicating that the early response does not require parasite invasion. Later during infection, genes involved in numerous host cell processes, inc luding 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 ind uce 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.