Veterinary and Biomedical Sciences, Department of

 

Document Type

Article

Date of this Version

2022

Citation

Lasrado et al., iScience 25, 103865 March 18, 2022 ª 2022 The Author(s). https://doi.org/10.1016/ j.isci.2022.103865

Comments

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Abstract

Coxsackievirus B3 (CVB3)-induced myocarditis is commonly employed to study viral pathogenesis in mice.Chronically affected micemaydevelop 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 thatM2cells, T cells, and fibroblasts may cooperatively or independently participate in the pathogenesis of viral myocarditis.

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