Toxoplasma gondii Dysregulates IFN-γ-Inducible Gene Expression in Human Fibroblasts: Insights from a Genome-Wide Transcriptional Profiling
| Autor: | John C. Boothroyd, Ashley E. Fouts, Seon-Kyeong Kim |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Immunology
Active Transport Cell Nucleus Interferon-gamma Neospora parasitic diseases Gene expression Animals Humans Immunology and Allergy Gene Regulatory Networks STAT1 Phosphorylation Gene Oligonucleotide Array Sequence Analysis Cell Nucleus biology Microarray analysis techniques Gene Expression Profiling Intracellular parasite Histocompatibility Antigens Class II Toxoplasma gondii Fibroblasts biology.organism_classification Neospora caninum Cell biology STAT1 Transcription Factor Gene Expression Regulation biology.protein Toxoplasma Interferon Regulatory Factor-1 |
| Zdroj: | The Journal of Immunology. 178:5154-5165 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.178.8.5154 |
| Popis: | Toxoplasma gondii is an obligate intracellular parasite that persists for the life of a mammalian host. The parasite’s ability to block the potent IFN-γ response may be one of the key mechanisms that allow Toxoplasma to persist. Using a genome-wide microarray analysis, we show here a complete dysregulation of IFN-γ-inducible gene expression in human fibroblasts infected with Toxoplasma. Notably, 46 of the 127 IFN-γ-responsive genes were induced and 19 were suppressed in infected cells before they were exposed to IFN-γ, indicating that other stimuli produced during infection may also regulate these genes. Following IFN-γ treatment, none of the 127 IFN-γ-responsive genes could be significantly induced in infected cells. Immunofluorescence assays showed at single-cell levels that infected cells, regardless of which Toxoplasma strain was used, could not be activated by IFN-γ to up-regulate the expression of IFN regulatory factor 1, a transcription factor that is under the direct control of STAT1, whereas uninfected cells in the same culture expressed IFN regulatory factor 1 normally in response to IFN-γ. STAT1 trafficked to the nucleus normally and indistinguishably in all uninfected and infected cells treated with IFN-γ, indicating that the inhibitory effects of Toxoplasma infection likely occur via blocking STAT1 transcriptional activity in the nucleus. In contrast, a closely related apicomplexan, Neospora caninum, was unable to inhibit IFN-γ-induced gene expression. A differential ability to interfere with the IFN-γ response may, in part, account for the differences in the pathogenesis seen among Toxoplasma and Neospora parasite strains. |
| Databáze: | OpenAIRE |
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