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Transcriptomic analysis reveals Toxoplasma gondii strain-specific differences in host cell response to dense granule protein GRA15

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Abstract

Growth and replication of the protozoan parasite Toxoplasma gondii within host cell entail the production of several effector proteins, which the parasite exploits for counteracting the host’s immune response. Despite considerable research to define the host signaling pathways manipulated by T. gondii and their effectors, there has been limited progress into understanding how individual members of the dense granule proteins (GRAs) modulate gene expression within host cells. The aim of this study was to evaluate whether T. gondii GRA15 protein plays any role in regulating host gene expression. Baby hamster kidney cells (BHK-21) were transfected with plasmids encoding GRA15 genes of either type I GT1 strain (GRA15I) or type II PRU strain (GRA15II). Gene expression patterns of transfected and nontransfected BHK-21 cells were investigated using RNA-sequencing analysis. GRA15I and GRA15II induced both known and novel transcriptional changes in the transfected BHK-21 cells compared with nontransfected cells. Pathway analysis revealed that GRA15II was mainly involved in the regulation of tumor necrosis factor (TNF), NF-κB, HTLV-I infection, and NOD-like receptor signaling pathways. GRA15I preferentially influenced the synthesis of unsaturated fatty acids in host cells. Our findings support the hypothesis that certain functions of GRA15 protein are strain dependent and that GRA15 modulates the expression of signaling pathways and genes with important roles in T. gondii pathophysiology. A greater understanding of host signaling pathways influenced by T. gondii effectors would allow the development of more efficient anti-T. gondii therapeutic schemes, capitalizing on disrupting parasite virulence factors to advance the treatment of toxoplasmosis.

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Acknowledgements

Project support was provided by the National Key Research and Development Program of China (Grant No. 2017YFD0500403), the International Science and Technology Cooperation Project of Gansu Province (Grant No. 17JR7WA031), National Natural Science Foundation of China (Grant No. 31230073), and the Elite Program of Chinese Academy of Agricultural Sciences. We thank Novogene Corporation for the technical assistance.

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Authors and Affiliations

  1. 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, Gansu Province, 730046, People’s Republic of China

    Qing Liu, Jun-Jun He, Fa-Cai Li, Wen-Bin Yang & Xing-Quan Zhu

  2. College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi Province, 030801, People’s Republic of China

    Qing Liu & Wen-Wei Gao

  3. Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK

    Hany M. Elsheikha

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  1. Qing Liu
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Correspondence to Jun-Jun He.

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Additional file 1

Gene expression profiling based on Fragments per Kilobase per Million mapped reads (FPKM) values. (XLS 2300 kb)

Additional file 2

Gene expression analysis of RNA-seq data, showing DEGs between BHK-21 cells transfected with pCMV-GRA15I and control BHK-21 cells transfected with pCMV-mCherry. (XLS 13 kb)

Additional file 3

Gene expression analysis of RNA-seq data, showing DEGs between BHK-21 cells transfected with pCMV-GRA15II and control BHK-21 cells transfected with pCMV-mCherry. (XLS 374 kb)

Additional file 4

Gene expression analysis of RNA-seq data, showing DEGs between BHK-21 cells transfected with pCMV-GRA15I and BHK-21 cells transfected with pCMV-GRA15II. (XLS 13 kb)

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Liu, Q., Gao, WW., Elsheikha, H.M. et al. Transcriptomic analysis reveals Toxoplasma gondii strain-specific differences in host cell response to dense granule protein GRA15. Parasitol Res 117, 2785–2793 (2018). https://doi.org/10.1007/s00436-018-5966-8

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  • DOI: https://doi.org/10.1007/s00436-018-5966-8

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