Dynamic immune ecosystem of dengue infection revealed by single-cell sequencing

Dengue is the most common human arboviral disease worldwide, which can result in severe complications. A dysfunctional immune response in dengue infective patients is a recurrent theme impacting symptoms and mortality, but the heterogeneity and dynamics of immune infiltrates during dengue infection remain poorly characterized. Here, we identified the immune cell types in scRNA-seq data from 13127 cells of 10 dengue infective patients and discovered the dynamic immune ecosystems of dengue infection. Notably, genes that exhibited higher expression in specific cell types play important roles in response to virus infection in a module manner. Transcription factors (TFs) are the major regulators (i.e., PAX5, IRF7, KLF4, and IRF8) that can potentially regulate infection-related genes. We demonstrated that the dynamic rewired regulatory network during dengue infection. Moreover, our data revealed the complex cell-cell communications from control to fever and severe dengue patients and prevalent cell-cell communication rewiring was observed. We further identified the IFN-II and CXCL signaling pathways that medicated the communications and play important roles in dengue infection. Together, our comprehensive analysis of dynamic immune ecosystem of dengue infection provided novel insights for understanding the pathogenesis of and developing effective therapeutic strategies for dengue infection.