Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany.
Genome Competence Center, Department of MFI, Robert Koch Institute, Berlin, Germany.
Front Immunol. 2023 Nov 23;14:1192057. doi: 10.3389/fimmu.2023.1192057. eCollection 2023.
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.
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。