Li Jie-Xi, He Jun-Jun, Elsheikha Hany M, Chen Dan, Zhai Bin-Tao, Zhu Xing-Quan, Yan Hai-Kuo
College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, Guangdong Province, People's Republic of China.
State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, Gansu Province, People's Republic of China.
Parasitol Res. 2019 Mar;118(3):783-792. doi: 10.1007/s00436-019-06215-y. Epub 2019 Jan 23.
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.
刚地弓形虫分泌一组棒状体分泌激酶（ROPs），它们在促进细胞内感染中发挥重要作用。刚地弓形虫棒状体细胞器蛋白17（ROP17）是这些重要效应蛋白之一。然而，其在感染过程中调节宿主细胞反应的作用仍知之甚少。在此，我们揭示ROP17（I型基因型）可诱导宿主细胞表达基因和转录因子发生显著变化。用PCMV-N-HA-ROP17质粒或空载体对照PCMV-N-HA质粒转染HEK293T细胞。转录组分析显示，在转染PCMV-N-HA-ROP17的HEK293T细胞中有3138个差异表达基因（DEGs），其中1456个上调，1682个下调。此外，这些差异表达基因中有715个是转录因子（TFs），包括423个下调的TFs和292个上调的TFs。大多数差异表达的TFs，无论属于信号转导、癌症相关途径还是免疫相关途径，在表达ROP17的细胞中均下调。ROP17还减少了宿主细胞中的可变剪接事件，推测是通过改变参与可变剪接途径的基因表达来实现的。综上所述，我们的研究结果提示了一种新的策略，即刚地弓形虫ROP17通过重新编程宿主基因表达来操纵各种细胞过程，包括免疫反应，以促进其在受感染宿主细胞中的定植和存活。
