Single-cell RNA-Seq reveals the cellular heterogeneity and molecular reprogramming of host response during influenza acute lung injury. Mus musculus

We performed a single cell RNA sequencing analysis of total lung cells from severe influenza disease to examine the cellular heterogeneity and cell-specific regulation of host response. We observed that IAV infection resulted in significant myelopoiesis, predominantly monocyte and macrophage subsets, which constituted over 50% of total immune cells. IAV infection resulted in the significant loss of endothelial and fibroblast cells, representing the most predominant non-hematopoietic cells and crucial to regulating inflammatory response and barrier integrity. We also show the cell-cell communication dynamics of interferon and chemokine signaling and global regulation of these responses in transition from homeostatic to IAV infection state. These data highlight robustly applying single cell RNA sequencing technology in establishing the atlas of cellular heterogeneity from its homeostatic transition to infection state and the host response regulation in IAV-mediated lung pathology.