Single Cell Transcriptomes of In Vitro Bradyzoite Infected Cells Reveals Toxoplasma gondii Stage Dependent Host Cell Alterations.
Single Cell Transcriptomes of In Vitro Bradyzoite Infected Cells Reveals Toxoplasma gondii Stage Dependent Host Cell Alterations.
复制标题
DOI：
10.3389/fcimb.2022.848693
复制
发表时间：
2022
影响因子：
5.7
通讯作者：
Yamagishi J
中科院分区：
文献类型：
--
作者：
Sugi T;Tomita T;Kidaka T;Kawai N;Hayashida K;Weiss LM;Yamagishi J
弓形虫缓殖子在其宿主细胞内建立慢性感染。最近的研究表明，一些寄生虫效应蛋白易位到宿主细胞在缓殖子阶段的慢性感染。为了了解宿主细胞和缓殖子在转录组水平上的相互作用，我们利用单细胞RNA测序（scRNA-Seq）来表征缓殖子诱导的宿主细胞反应。在感染的宿主、具有低寄生虫映射读数的细胞和模拟（未暴露）对照细胞中观察到不同的基因表达谱。基因集富集分析显示，感染后c-Myc和NF-κB信号通路及能量代谢途径均上调。与未暴露的宿主对照细胞相比，I型和II型干扰素应答途径在具有低寄生虫定位读数的细胞中上调，并且这种上调效应在感染的细胞中逆转。在宿主细胞中观察到的差异取决于寄生虫的分化状态，如通过BAG 1和SAG 1表达所确定的。NF-κB、炎症反应途径和IFN-γ反应途径在含有T. gondii BAG 1 +/SAG 1-，而这种下调作用在T.弓形虫BAG 1 −/SAG 1+。我们还确定了两个不同的宿主细胞亚群，含有T。弓形虫BAG 1 +/SAG 1-，其中一个显示不同的转录组，上调c-Myc表达。总体而言，这些数据清楚地表明，宿主细胞的转录改变由缓殖子感染是不同的速殖子感染，表明微调的宿主免疫反应。
Toxoplasma gondii bradyzoites establish chronic infections within their host cells. Recent studies have demonstrated that several parasite effector proteins are translocated to host cells during the bradyzoite stage of chronic infection. To understand the interaction between host cells and bradyzoites at the transcriptomic landscape level, we utilized single-cell RNA-sequencing (scRNA-Seq) to characterize the bradyzoite-induced host cell response. Distinct gene expression profiles were observed in infected host, cells with low parasite mapped reads, and mock (non-exposed) control cells. Gene set enrichment analysis showed that c-Myc and NF-κB signaling and energy metabolic pathways were upregulated by infection. Type I and II interferon response pathways were upregulated in cells with low parasite mapped reads compared to the non-exposed host control cells, and this upregulation effect was reversed in infected cells. Differences were observed in the host cells depending on the differentiation status of the parasites, as determined by BAG1 and SAG1 expression. NF-κB, inflammatory response pathways, and IFN-γ response pathways were downregulated in host cells containing T. gondii BAG1+/SAG1−, whereas this downregulation effect was reversed in case of T. gondii BAG1−/SAG1+. We also identified two distinct host cell subsets that contained T. gondii BAG1+/SAG1−, one of which displayed distinct transcriptomes with upregulated c-Myc expression. Overall, these data clearly demonstrate that host cell transcriptional alteration by bradyzoite infection is different from that of tachyzoite infection, indicating fine-tuning of the host immune response.