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大鼠巨细胞病毒能在树突状细胞中有效复制,并诱导其转录谱发生变化。

Rat cytomegalovirus efficiently replicates in dendritic cells and induces changes in their transcriptional profile.

机构信息

Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany.

Genome Competence Center, Department of MFI, Robert Koch Institute, Berlin, Germany.

出版信息

Front Immunol. 2023 Nov 23;14:1192057. doi: 10.3389/fimmu.2023.1192057. eCollection 2023.

Abstract

Dendritic cells (DC) play a crucial role in generating and maintaining antiviral immunity. While DC are implicated in the antiviral defense by inducing T cell responses, they can also become infected by Cytomegalovirus (CMV). CMV is not only highly species-specific but also specialized in evading immune protection, and this specialization is in part due to characteristic genes encoded by a given virus. Here, we investigated whether rat CMV can infect XCR1 DC and if infection of DC alters expression of cell surface markers and migration behavior. We demonstrate that wild-type RCMV and a mutant virus lacking the γ-chemokine ligand ( RCMV infect splenic rat DC and identify viral assembly compartments. Replication-competent RCMV reduced XCR1 and MHCII surface expression. Further, gene expression of infected DC was analyzed by bulk RNA-sequencing (RNA-Seq). RCMV infection reverted a state of DC activation that was induced by DC cultivation. On the functional level, we observed impaired chemotactic activity of infected XCR1 DC compared to mock-treated cells. We therefore speculate that as a result of RCMV infection, DC exhibit diminished XCR1 expression and are thereby blocked from the lymphocyte crosstalk.

摘要

树突状细胞 (DC) 在产生和维持抗病毒免疫方面发挥着关键作用。虽然 DC 通过诱导 T 细胞反应来参与抗病毒防御,但它们也可能被巨细胞病毒 (CMV) 感染。CMV 不仅具有高度的物种特异性,而且还专门逃避免疫保护,这种专门化部分归因于特定病毒编码的特征基因。在这里,我们研究了大鼠 CMV 是否可以感染 XCR1 DC,以及 DC 的感染是否会改变细胞表面标记物的表达和迁移行为。我们证明野生型 RCMV 和一种缺乏 γ-趋化因子配体 (RCMV) 的突变病毒感染脾大鼠 DC,并鉴定了病毒组装区室。复制型 RCMV 降低了 XCR1 和 MHCII 的表面表达。此外,通过批量 RNA 测序 (RNA-Seq) 分析了感染 DC 的基因表达。RCMV 感染使由 DC 培养诱导的 DC 激活状态逆转。在功能水平上,我们观察到与 mock 处理的细胞相比,感染的 XCR1 DC 的趋化活性受损。因此,我们推测由于 RCMV 感染,DC 表现出 XCR1 表达的减少,从而阻止了淋巴细胞的相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c775/10702230/0a725e17ecef/fimmu-14-1192057-g001.jpg

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