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 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 approximately 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.
Blader
I J
IJ
Department of Microbiology and Immunology, Stanford University, Stanford, California 94305-5124, USA.
Manger
I D
ID
Boothroyd
J C
JC
D000818:Animals; D001685:Biological Factors / Q000494:pharmacology; D015152:Blotting, Northern; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D020869:Gene Expression Profiling; D006019:Glycolysis; D006790:Host-Parasite Interactions; D006801:Humans; D008798:Mevalonic Acid / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D013185:Squalene / Q000031:analogs & derivatives / Q000378:metabolism; D014122:Toxoplasma / Q000472:pathogenicity*; D015854:Up-Regulation
D001685:Biological Factors; D017077:Culture Media, Conditioned; D016207:Cytokines; D012333:RNA, Messenger; D013185:Squalene; D002784:Cholesterol; C019556:squalane; D008798:Mevalonic Acid