Heterogeneity of lymphoid cells in PBMCs in the acute phase of SFTS: Single-cell transcriptome profiling

Abstract

Severe fever with thrombocytopenia syndrome (SFTS), caused by Dabie bandavirus (DBV), triggers aberrant immune activation and cytokine storms, contributing to poor prognosis; however, its immune dysfunction mechanism remains unclear. Current management relies on symptomatic treatment and glucocorticoids, but no standardized treatment guidelines exist. This study investigated the mechanisms of abnormal lymphocyte function in acute-phase SFTS and the effects of glucocorticoid treatment on lymphoid cells using single-cell RNA sequencing (scRNA-seq) and bioinformatics analysis. We enrolled three healthy volunteers and 13 patients with acute SFTS and divided them into four groups. ScRNA-seq was performed on peripheral blood mononuclear cells from all 16 participants, capturing transcripts from the 3′ ends of mRNA. Bioinformatics analyses were used to profile patient immunological signatures, characterize subpopulation compositions, infer developmental trajectories, and assess lymphoid cell interactions. We obtained 120886 lymphoid cells, which were clustered into 23 functionally heterogeneous subsets. Results showed that patients with severe SFTS exhibited stronger inflammatory and adaptive immune responses. Glucocorticoid treatment suppressed inflammation and the interferon response but also inhibited the production of virus-specific antibodies. These findings suggest that appropriate glucocorticoid administration may alleviate the hyperinflammatory state in severe SFTS during the acute phase, although it is not recommended as a conventional treatment because of its potential to suppress antiviral immunity. This study provides insights into SFTS immunopathology and informs the optimized clinical use of glucocorticoids.

Keywords

thrombocytopenia syndrome / Dabie bandavirus / single-cell RNA sequencing / lymphoid cells / glucocorticoid

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81871242), the "YiQi" Fund Project (Grant Nos. 2024YQZL01 and 2023YQFH05), and the National Key Research and Development Program of China (Grant No. 2022YFF0710100).

Acknowledgments

We thank the subjects for donating the blood sample used in our study. We thank the staff of Singleron (Nanjing, Jiangsu, China) for the service of single-cell transcriptome sequencing from the 3′ end of mRNA.

Additional information

The online version contains supplementary material available at http://www.jbr-pub.org.cn/article/doi/10.7555/JBR.39.20250250?pageType=en.

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