Analysis of SFTS pathogenesis based on single-cell RNA sequencing of monocytes

Abstract

BackgroudSevere fever with thrombocytopenia syndrome (SFTS) is a newly identified tick-borne viral disease with a high mortality rate. Monocytes are known to play an important role in the pathogenesis of SFTS, but the distinct subpopulations of monocytes associated with the disease progression and their roles in inflammatory responses remain unclear. In this study, we used single-cell RNA sequencing (scRNA-seq) to explore the specific monocyte subpopulations correlated with the progression of SFTS and their involvement in inflammatory processes. MethodsscRNA-seq analysis was conducted on isolated monocytes from seven SFTS patients, validated by cell identification through flow cytometry. Comparative analyses were performed using three normal monocyte samples from public databases. Bioinformatic tools including Cell Ranger, Seurat, Monocle 2, GSEA, and SCENIC were utilized to identify distinct cell populations and transcriptional patterns. ResultsOur results indicate that severe SFTS patients in the ICU exhibited a reduced proportion of circulating HLA-DR+CD14+ monocytes compared to non-severe hospitalized SFTS patients, indicating a dysfunctional immune response. Increased numbers of CD163+CD14+ monocytes in acute SFTS patients correlated with disease severity. CD163+CD14+ monocytes were identified as potential target cells for SFTSV infection. SFTSV infection could drive monocyte differentiation into the M2 phenotype, promoting virus persistence and disease advancement. ConclusionOur studies in SFTS patients have shown that monocytes are target cells for SFTSV. Notably, an expansion of CD163+CD14+ monocytes in SFTS has been shown to be associated with severe clinical disease. In addition, activated IL-6/JAK/STAT3 signaling in SFTS patients induced CD163+CD14+ monocyte expansion, which was recovered by tofacitinib treatment.