CLC number:
On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 2022-04-19
Cited: 0
Clicked: 1813
Citations: Bibtex RefMan EndNote GB/T7714
Kaige DU, Fei LU, Chengzuo XIE, Haojie DING, Yu SHEN, Yafan GAO, Shaohong LU, Xunhui ZHUO. Toxoplasma gondii infection induces cell apoptosis via multiple pathways revealed by transcriptome analysis[J]. Journal of Zhejiang University Science B, 2022, 23(4): 315-327.
@article{title="Toxoplasma gondii infection induces cell apoptosis via multiple pathways revealed by transcriptome analysis",
author="Kaige DU, Fei LU, Chengzuo XIE, Haojie DING, Yu SHEN, Yafan GAO, Shaohong LU, Xunhui ZHUO",
journal="Journal of Zhejiang University Science B",
volume="23",
number="4",
pages="315-327",
year="2022",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2100877"
}
%0 Journal Article
%T Toxoplasma gondii infection induces cell apoptosis via multiple pathways revealed by transcriptome analysis
%A Kaige DU
%A Fei LU
%A Chengzuo XIE
%A Haojie DING
%A Yu SHEN
%A Yafan GAO
%A Shaohong LU
%A Xunhui ZHUO
%J Journal of Zhejiang University SCIENCE B
%V 23
%N 4
%P 315-327
%@ 1673-1581
%D 2022
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2100877
TY - JOUR
T1 - Toxoplasma gondii infection induces cell apoptosis via multiple pathways revealed by transcriptome analysis
A1 - Kaige DU
A1 - Fei LU
A1 - Chengzuo XIE
A1 - Haojie DING
A1 - Yu SHEN
A1 - Yafan GAO
A1 - Shaohong LU
A1 - Xunhui ZHUO
J0 - Journal of Zhejiang University Science B
VL - 23
IS - 4
SP - 315
EP - 327
%@ 1673-1581
Y1 - 2022
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2100877
Abstract: Toxoplasma gondii is a worldwide parasite that can infect almost all kinds of mammals and cause fatal toxoplasmosis in immunocompromised patients. apoptosis is one of the principal strategies of host cells to clear pathogens and maintain organismal homeostasis, but the mechanism of cell apoptosis induced by T. gondii remains obscure. To explore the apoptosis influenced by T. gondii, Vero cells infected or uninfected with the parasite were subjected to apoptosis detection and subsequent dual RNA sequencing (RNA-seq). Using high-throughput Illumina sequencing and bioinformatics analysis, we found that pro-apoptosis genes such as DNA damage-inducible transcript 3 (DDIT3), growth arrest and DNA damage-inducible α (GADD45A), caspase-3 (CASP3), and high-temperature requirement protease A2 (HtrA2) were upregulated, and anti-apoptosis genes such as poly(adenosine diphosphate (ADP)-ribose) polymerase family member 3 (PARP3), B-cell lymphoma 2 (Bcl-2), and baculoviral inhibitor of apoptosis protein (IAP) repeat containing 5 (BIRC5) were downregulated. Besides, tumor necrosis factor (TNF) receptor-associated factor 1 (TRAF1), TRAF2, TNF receptor superfamily member 10b (TNFRSF10b), disabled homolog 2 (DAB2)-interacting protein (DAB2IP), and inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) were enriched in the upstream of TNF, TNF-related apoptosis-inducing ligand (TRAIL), and endoplasmic reticulum (ER) stress pathways, and TRAIL-receptor 2 (TRAIL-R2) was regarded as an important membrane receptor influenced by T. gondii that had not been previously considered. In conclusion, the T. gondii RH strain could promote and mediate apoptosis through multiple pathways mentioned above in Vero cells. Our findings improve the understanding of the T. gondii infection process through providing new insights into the related cellular apoptosis mechanisms.
[1]AngeloniMB, GuirelliPM, FrancoPS, et al., 2013. Differential apoptosis in BeWo cells after infection with highly (RH) or moderately (ME49) virulent strains of Toxoplasma gondii is related to the cytokine profile secreted, the death receptor fas expression and phosphorylated ERK1/2 expression. Placenta, 34(11):973-982.
[2]AriyasuD, YoshidaH, HasegawaY, 2017. Endoplasmic reticulum (ER) stress and endocrine disorders. Int J Mol Sci, 18(2):382.
[3]BaderGD, HogueCWV, 2003. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics, 4:2.
[4]ChinCH, ChenSH, WuHH, et al., 2014. CytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol, 8(S4):S11.
[5]CongW, DottoriniT, KhanF, et al., 2018. Acute Toxoplasma gondii infection in cats induced tissue-specific transcriptional response dominated by immune signatures. Front Immunol, 9:2403.
[6]CuiJM, ShenB, 2020. Transcriptomic analyses reveal distinct response of porcine macrophages to Toxoplasma gondii infection. Parasitol Res, 119(6):1819-1828.
[7]DelavalléeL, MathiahN, CabonL, et al., 2020. Mitochondrial AIF loss causes metabolic reprogramming, caspase-independent cell death blockade, embryonic lethality, and perinatal hydrocephalus. Mol Metab, 40:101027.
[8]EnariM, SakahiraH, YokoyamaH, et al., 1998. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature, 391(6662):43-50.
[9]EstaquierJ, ValletteF, VayssiereJL, et al., 2012. The mitochondrial pathways of apoptosis. In: Scatena R, Bottoni P, Giardina B (Eds.), Advances in Mitochondrial Medicine. Springer, Dordrecht, p.157-183.
[10]FoxBA, BzikDJ, 2015. Nonreplicating, cyst-defective type II Toxoplasma gondii vaccine strains stimulate protective immunity against acute and chronic infection. Infect Immun, 83(5):2148-2155.
[11]GaoM, GuoN, HuangCS, et al., 2009. Diverse roles of GADD45α in stress signaling. Curr Protein Pept Sci, 10(4):388-394.
[12]HillRD, GouffonJS, SaxtonAM, et al., 2012. Differential gene expression in mice infected with distinct Toxoplasma strains. Infect Immun, 80(3):968-974.
[13]HuYY, BiY, YaoDH, et al., 2019. Omi/HtrA2 protease associated cell apoptosis participates in blood-brain barrier dysfunction. Front Mol Neurosci, 12:48.
[14]IharaF, FereigRM, HimoriY, et al., 2020. Toxoplasma gondii dense granule proteins 7, 14, and 15 are involved in modification and control of the immune response mediated via Nf-κB pathway. Front Immunol, 11:1709.
[15]KimCM, ParkHH, 2020. Comparison of target recognition by TRAF1 and TRAF2. Int J Mol Sci, 21(8):2895.
[16]LimaTS, LodoenMB, 2019. Mechanisms of human innate immune evasion by Toxoplasma gondii. Front Cell Infect Microbiol, 9:103.
[17]LinYC, ShenZR, SongXH, et al., 2018. Comparative transcriptomic analysis reveals adriamycin-induced apoptosis via p53 signaling pathway in retinal pigment epithelial cells. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(12):895-909.
[18]LivakKJ, SchmittgenTD, 2001. Analysis of relative gene expression data using real-time quantitative PCR and the2-ΔΔCT method. Methods, 25(4):402-408.
[19]LossiL, CastagnaC, MerighiA, 2018. Caspase-3 mediated cell death in the normal development of the mammalian cerebellum. Int J Mol Sci, 19(12):3999.
[20]LuG, ZhouJ, ZhaoYH, et al., 2019. Transcriptome sequencing investigated the tumor-related factors changes after T. Gondii infection. Front Microbiol, 10:181.
[21]MammariN, HalabiMA, YaacoubS, et al., 2019. Toxoplasma gondii modulates the host cell responses: an overview of apoptosis pathways. Biomed Res Int, 2019:6152489.
[22]ManglaA, GuerraMT, NathansonMH, 2020. Type 3 inositol 1,4,5-trisphosphate receptor: a calcium channel for all seasons. Cell Calcium, 85:102132.
[23]ParlogA, SchlüterD, DunayIR, 2015. Toxoplasma gondii-induced neuronal alterations. Parasite Immunol, 37(3):159-170.
[24]QuanJH, ChaGH, ZhouW, et al., 2013. Involvement of PI 3 kinase/Akt-dependent Bad phosphorylation in Toxoplasma gondii-mediated inhibition of host cell apoptosis. Exp Parasitol, 133(4):462-471.
[25]RajedadramA, PinKY, LingSK, et al., 2021. Hydroxychavicol, a polyphenol from Piper betle leaf extract, induces cell cycle arrest and apoptosis in TP53-resistant HT-29 colon cancer cells. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 22(2):112-122.
[26]RanjanA, IwakumaT, 2016. Non-canonical cell death induced by p53. Int J Mol Sci, 17(12):2068.
[27]RosowskiEE, SaeijJPJ, 2012. Toxoplasma gondii clonal strains all inhibit STAT1 transcriptional activity but polymorphic effectors differentially modulate IFNγ induced gene expression and STAT1 phosphorylation. PLoS ONE, 7(12):e51448.
[28]RosowskiEE, LuD, JulienL, et al., 2011. Strain-specific activation of the NF-κB pathway by GRA15, a novel Toxoplasma gondii dense granule protein. J Exp Med, 208(1):195-212.
[29]SajjadN, MirMM, KhanJ, et al., 2019. Recognition of TRAIP with TRAFs: current understanding and associated diseases. Int J Biochem Cell Biol, 115:105589.
[30]SzklarczykD, FranceschiniA, WyderS, et al., 2015. STRING v10: Protein–protein interaction networks, integrated over the tree of life. Nucleic Acids Res, 43(D1):D447-D452.
[31]TantralL, MalathiK, KohyamaS, et al., 2004. Intracellular calcium release is required for caspase-3 and -9 activation. Cell Biochem Funct, 22(1):35-40.
[32]VenugopalK, MarionS, 2018. Secretory organelle trafficking in Toxoplasma gondii: a long story for a short travel. Int J Med Microbiol, 308(7):751-760.
[33]WanLJ, GongLL, WangW, et al., 2015. T. Gondii rhoptry protein ROP18 induces apoptosis of neural cells via endoplasmic reticulum stress pathway. Parasit Vectors, 8:554.
[34]WangT, ZhouJ, GanXF, et al., 2014. Toxoplasma gondii induce apoptosis of neural stem cells via endoplasmic reticulum stress pathway. Parasitology, 141(7):988-995.
[35]WeiW, ZhangFF, ChenH, et al., 2018. Toxoplasma gondii dense granule protein 15 induces apoptosis in choriocarcinoma JEG-3 cells through endoplasmic reticulum stress. Parasit Vectors, 11(1):251.
[36]YangZS, HouYH, HaoTF, et al., 2017. A human proteome array approach to identifying key host proteins targeted by Toxoplasma kinase ROP18. Mol Cell Proteomics, 16(3):469-484.
[37]YuanX, GajanA, ChuQ, et al., 2018. Developing TRAIL/TRAIL death receptor-based cancer therapies. Cancer Metastasis Rev, 37(4):733-748.
[38]ZhouCX, ElsheikhaHM, ZhouDH, et al., 2016. Dual identification and analysis of differentially expressed transcripts of porcine PK-15 cells and Toxoplasma gondii during in vitro infection. Front Microbiol, 7:721.
[39]ZhouLJ, ChenM, PuthiyakunnonS, et al., 2019. Toxoplasma gondii ROP18 inhibits human glioblastoma cell apoptosis through a mitochondrial pathway by targeting host cell P2X1. Parasit Vectors, 12:284.
[40]ZhuoXH, SunHC, HuangB, et al., 2017. Evaluation of potential anti-toxoplasmosis efficiency of combined traditional herbs in a mouse model. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 18(6):453-461.
Open peer comments: Debate/Discuss/Question/Opinion
<1>