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转录组分析揭示,感染通过多种途径诱导细胞凋亡。

infection induces cell apoptosis via multiple pathways revealed by transcriptome analysis.

机构信息

School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou 310053, China.

Shandong Center for Disease Control and Prevention, Jinan 250021, China.

出版信息

J Zhejiang Univ Sci B. 2022 Apr 15;23(4):315-327. doi: 10.1631/jzus.B2100877.

Abstract

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 remains obscure. To explore the apoptosis influenced by , 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 (), growth arrest and DNA damage-inducible α (), caspase-3 (), and high-temperature requirement protease A2 () were upregulated, and anti-apoptosis genes such as poly(adenosine diphosphate (ADP)-ribose) polymerase family member 3 (), B-cell lymphoma 2 (), and baculoviral inhibitor of apoptosis protein (IAP) repeat containing 5 () were downregulated. Besides, tumor necrosis factor (TNF) receptor-associated factor 1 (), , TNF receptor superfamily member 10b (), disabled homolog 2 (DAB2)‍-interacting protein (), and inositol 1,4,5-trisphosphate receptor type 3 () 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 that had not been previously considered. In conclusion, the RH strain could promote and mediate apoptosis through multiple pathways mentioned above in Vero cells. Our findings improve the understanding of the infection process through providing new insights into the related cellular apoptosis mechanisms.

摘要

刚地弓形虫是一种全球性寄生虫,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起致命的弓形体病。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,但弓形虫感染诱导细胞凋亡的机制尚不清楚。为了研究弓形虫感染对细胞凋亡的影响,我们用未感染和感染弓形虫的 Vero 细胞进行凋亡检测和随后的双 RNA 测序(RNA-seq)。通过高通量 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()、生长停滞和 DNA 损伤诱导α()、半胱天冬酶-3()和高温需求蛋白酶 A2()上调,而抗凋亡基因如多聚(腺苷二磷酸(ADP)-核糖)聚合酶家族成员 3()、B 细胞淋巴瘤 2()和杆状病毒凋亡蛋白抑制剂(IAP)重复包含 5()下调。此外,肿瘤坏死因子(TNF)受体相关因子 1()、TNF 受体超家族成员 10b()、Disabled homolog 2(DAB2)相互作用蛋白()、三磷酸肌醇受体类型 3()在 TNF、TNF 相关凋亡诱导配体(TRAIL)和内质网(ER)应激途径的上游富集,而 TRAIL 受体 2(TRAIL-R2)被认为是一个重要的膜受体,受弓形虫影响,以前未被考虑。总之,RH 株可通过上述多种途径在 Vero 细胞中促进和介导凋亡。我们的研究结果通过提供细胞凋亡相关机制的新见解,提高了对弓形虫感染过程的认识。

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