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Single Cell Transcriptomes of In Vitro Bradyzoite Infected Cells Reveals Toxoplasma gondii Stage Dependent Host Cell Alterations

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Title: Single Cell Transcriptomes of In Vitro Bradyzoite Infected Cells Reveals Toxoplasma gondii Stage Dependent Host Cell Alterations
Authors: Sugi, Tatsuki Browse this author
Tomita, Tadakimi Browse this author
Kidaka, Taishi Browse this author
Kawai, Naoko Browse this author
Hayashida, Kyoko Browse this author
Weiss, Louis M. Browse this author
Yamagishi, Junya Browse this author →KAKEN DB
Keywords: Toxoplasma gondii
host-pathogen interaction
chronic infection
single cell transcriptome
Issue Date: 14-Mar-2022
Publisher: Frontiers Media
Journal Title: Frontiers in Cellular and Infection Microbiology
Volume: 12
Start Page: 848693
Publisher DOI: 10.3389/fcimb.2022.848693
Abstract: 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-kappa B 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-kappa B, inflammatory response pathways, and IFN-gamma 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.
Type: article
Appears in Collections:人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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