Lasrado Ninaad, Borcherding Nicholas, Arumugam Rajkumar, Starr Timothy K, Reddy Jay
School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
Department of Pathology and Immunology, Washington University in St. Louis, St Louis, MO 63130, USA.
iScience. 2022 Feb 2;25(3):103865. doi: 10.1016/j.isci.2022.103865. eCollection 2022 Mar 18.
Coxsackievirus B3 (CVB3)-induced myocarditis is commonly employed to study viral pathogenesis in mice. Chronically affected mice may develop dilated cardiomyopathy, which may involve the mediation of immune and nonimmune cells. To dissect this complexity, we performed single-cell RNA sequencing on heart cells from healthy and myocarditic mice, leading us to note significant proportions of myeloid cells, T cells, and fibroblasts. Although the transcriptomes of myeloid cells were mainly of M2 phenotype, the Th17 cells, CTLs, and Treg cells had signatures critical for cytotoxic functions. Fibroblasts were heterogeneous expressing genes important in fibrosis and regulation of inflammation and immune responses. The intercellular communication networks revealed unique interactions and signaling pathways in the cardiac cellulome, whereas myeloid cells and T cells had upregulated unique transcription factors modulating cardiac remodeling functions. Together, our data suggest that M2 cells, T cells, and fibroblasts may cooperatively or independently participate in the pathogenesis of viral myocarditis.
柯萨奇病毒B3（CVB3）诱导的心肌炎常用于研究小鼠的病毒发病机制。长期受影响的小鼠可能会发展为扩张型心肌病，这可能涉及免疫细胞和非免疫细胞的介导作用。为了剖析这种复杂性，我们对健康小鼠和患心肌炎小鼠的心脏细胞进行了单细胞RNA测序，结果发现髓样细胞、T细胞和成纤维细胞占比显著。虽然髓样细胞的转录组主要呈现M2表型，但Th17细胞、细胞毒性T淋巴细胞（CTL）和调节性T细胞（Treg）具有对细胞毒性功能至关重要的特征。成纤维细胞具有异质性，表达在纤维化以及炎症和免疫反应调节中重要的基因。细胞间通讯网络揭示了心脏细胞组中独特的相互作用和信号通路，而髓样细胞和T细胞上调了调节心脏重塑功能的独特转录因子。总之，我们的数据表明M2细胞、T细胞和成纤维细胞可能协同或独立参与病毒性心肌炎的发病机制。
