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Toxoplasma gondii ROP17 inhibits the innate immune response of HEK293T cells to promote its survival

  • Jie-Xi Li
  • Jun-Jun He
  • Hany M. Elsheikha
  • Dan Chen
  • Bin-Tao Zhai
  • Xing-Quan ZhuEmail author
  • Hai-Kuo YanEmail author
Genetics, Evolution, and Phylogeny - Original Paper
  • 71 Downloads

Abstract

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.

Keywords

ROP17 Toxoplasma gondii Differential gene expression Transcriptome Innate immunity 

Notes

Acknowledgements

We thank BGI-Shenzhen Corporation for technical assistance.

Authors’ contributions

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.

Funding information

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

436_2019_6215_Fig10_ESM.png (38 kb)
Fig. S1

Western blot analysis of the transfected cells. (PNG 38 kb)

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High Resolution Image (TIF 161 kb)
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Fig. S2

Summary of the quality assessment of the sequencing raw reads. (PNG 104 kb)

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High Resolution Image (TIF 111 kb)
436_2019_6215_MOESM3_ESM.png (22 kb)
Fig. S3 mRNA surveillance pathway in ROP17-transfected HEK293T cells. Green and red colors represent downregulated and upregulated genes, respectively. (PNG 22 kb)
436_2019_6215_MOESM4_ESM.docx (19 kb)
Table S1 Primers used for qRT-PCR validation. (DOCX 19 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.College of Veterinary MedicineSouth China Agricultural UniversityGuangzhouPeople’s Republic of China
  2. 2.State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhouPeople’s Republic of China
  3. 3.Faculty of Medicine and Health Sciences, School of Veterinary Medicine and ScienceUniversity of NottinghamLoughboroughUK
  4. 4.Inner Mongolia Agriculture UniversityHohhotPeople’s Republic of China
  5. 5.Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and ZoonosesYangzhou University College of Veterinary MedicineYangzhouPeople’s Republic of China

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