Toxoplasma gondii infection induces cell apoptosis via multiple pathways revealed by transcriptome analysis
Toxoplasma gondii infection induces cell apoptosis via multiple pathways revealed by transcriptome analysis
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转录组分析揭示弓形虫感染通过多种途径诱导细胞凋亡
DOI：
10.1631/jzus.b2100877
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发表时间：
2022-04-01
影响因子：
5.1
通讯作者：
Zhuo, Xunhui
中科院分区：
文献类型：
--
作者：
Du, Kaige;Lu, Fei;Zhuo, Xunhui
刚地弓形虫是一种全球性的寄生虫，几乎可以感染所有种类的哺乳动物，并在免疫功能低下的患者中引发致命的弓形虫病。细胞凋亡是宿主细胞清除病原体和维持机体稳态的主要策略之一，但刚地弓形虫诱导细胞凋亡的机制仍不清楚。为了探究刚地弓形虫对细胞凋亡的影响，对感染和未感染该寄生虫的非洲绿猴肾细胞（Vero细胞）进行了细胞凋亡检测以及后续的双RNA测序（RNA - seq）。通过高通量的Illumina测序和生物信息学分析，我们发现促凋亡基因，如DNA损伤诱导转录物3（DDIT3）、生长停滞和DNA损伤诱导蛋白α（GADD45A）、半胱天冬酶 - 3（CASP3）和高温需求蛋白酶A2（HtrA2）表达上调，而抗凋亡基因，如多聚（二磷酸腺苷（ADP） - 核糖）聚合酶家族成员3（PARP3）、B细胞淋巴瘤2（Bcl - 2）和含杆状病毒凋亡抑制蛋白（IAP）重复序列5（BIRC5）表达下调。此外，肿瘤坏死因子（TNF）受体相关因子1（TRAF1）、TRAF2、肿瘤坏死因子受体超家族成员10b（TNFRSF10b）、Disabled同源物2（DAB2）相互作用蛋白（DAB2IP）和1,4,5 - 三磷酸肌醇受体3型（ITPR3）在TNF、肿瘤坏死因子相关凋亡诱导配体（TRAIL）和内质网（ER）应激通路的上游富集，并且TRAIL受体2（TRAIL - R2）被认为是一种受刚地弓形虫影响的重要膜受体，这在之前未被考虑到。总之，刚地弓形虫RH株可以通过上述多种途径在Vero细胞中促进和介导细胞凋亡。我们的研究结果通过为相关细胞凋亡机制提供新的见解，增进了对刚地弓形虫感染过程的理解。
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.