Toxoplasma gondii ROP17 inhibits the innate immune response of HEK293T cells to promote its survival
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Toxoplasma gondii secretes a group of rhoptry-secreted kinases (ROPs), which play significant roles in promoting intracellular infection. T. gondii rhoptry organelle protein 17 (ROP17) is one of these important effector proteins. However, its role in modulating host cell response during infection remains poorly understood. Here, we reveal that ROP17 (genotype I) induces significant changes in the expression genes and transcription factors of host cells. HEK293T cells were transfected with PCMV-N-HA-ROP17 plasmid or empty control PCMV-N-HA plasmid. Transcriptomic analysis revealed 3138 differentially expressed genes (DEGs) in PCMV-N-HA-ROP17-transfected HEK293T cells, including 1456 upregulated, 1682 downregulated DEGs. Also, 715 of the DEGs were transcription factors (TFs), including 423 downregulated TFs and 292 upregulated TFs. Most differentially expressed TFs, whether belong to signal transduction, cancer-related pathways or immune-related pathways, were downregulated in ROP17-expressing cells. ROP17 also decreased alternative splicing events in host cells, presumably via alteration of the expression of genes involved in the alternative splicing pathway. Taken together, our findings suggest a novel strategy whereby T. gondii ROP17 manipulates various cellular processes, including immune response through reprogramming host gene expression to promote its own colonization and survival in the infected host cells.
KeywordsROP17 Toxoplasma gondii Differential gene expression Transcriptome Innate immunity
We thank BGI-Shenzhen Corporation for technical assistance.
J.-J.H., X.-Q.Z., H.M.E, and H.-K.Y. conceived and designed the study, and critically revised the manuscript. J.-X.L. performed the experiment, analyzed the transcriptomic profile data and drafted the manuscript. D.C. and B.-T.Z. helped in study implementation and manuscript revision. All authors have read and approved the final manuscript.
Project support was provided by the National Key Research and Development Program of China (Grant No. 2017YFD0500403), by the International Science and Technology Cooperation Project of Gansu Provincial Key Research and Development Program (Grant No. 17JR7WA031), by National Natural Science Foundation of China (Grant No. 31230073), and by the Elite Program of Chinese Academy of Agricultural Sciences.
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Conflict of interest
The authors declare that they have no competing interests.
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