Cham Lamin B, Gunst Jesper D, Schleimann Mariane H, Frattari Giacomo S, Rosas-Umbert Miriam, Vibholm Line K, van der Sluis Renée M, Jakobsen Martin R, Olesen Rikke, Lin Lin, Tolstrup Martin, Søgaard Ole S
Department of Infectious Diseases, Aarhus University Hospital, 8200 Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark.
iScience. 2023 Aug 12;26(9):107628. doi: 10.1016/j.isci.2023.107628. eCollection 2023 Sep 15.
Human plasmacytoid dendritic cells (pDCs) play a central role in initiating and activating host immune responses during infection. To understand how the transcriptome of pDCs is impacted by HIV-1 infection and exogenous stimulation, we isolated pDCs from healthy controls, people with HIV-1 (PWH) before and during toll-like receptor 9 (TLR9) agonist treatment and performed single-cell (sc)-RNA sequencing. Our cluster analysis revealed four pDC clusters: pDC1, pDC2, cytotoxic-like pDC and an exhausted pDC cluster. The inducible cytotoxic-like pDC cluster is characterized by high expression of both antiviral and cytotoxic genes. Further analyses confirmed that cytotoxic-like pDCs are distinct from NK and T cells. Cell-cell communication analysis also demonstrated that cytotoxic-like pDCs exhibit similar incoming and outgoing cellular communicating signals as other pDCs. Thus, our study presents a detailed transcriptomic atlas of pDCs and provides new perspectives on the mechanisms of regulation and function of cytotoxic-like pDCs.
人类浆细胞样树突状细胞（pDCs）在感染期间启动和激活宿主免疫反应中发挥核心作用。为了解pDCs的转录组如何受到HIV-1感染和外源性刺激的影响，我们从健康对照、HIV-1感染者（PWH）在Toll样受体9（TLR9）激动剂治疗前和治疗期间分离出pDCs，并进行了单细胞（sc）RNA测序。我们的聚类分析揭示了四个pDC簇：pDC1、pDC2、细胞毒性样pDC和耗竭性pDC簇。可诱导的细胞毒性样pDC簇的特征是抗病毒和细胞毒性基因的高表达。进一步分析证实，细胞毒性样pDC与NK细胞和T细胞不同。细胞间通讯分析还表明，细胞毒性样pDC与其他pDC表现出相似的传入和传出细胞通讯信号。因此，我们的研究展示了pDCs的详细转录组图谱，并为细胞毒性样pDC的调控机制和功能提供了新的视角。
