Age-dependent immune responses and resident cell dynamics in young mice following pneumonia

Infancy represents a unique period of immune vulnerability. This study investigated age-specific immune dynamics associated with differential health outcomes in the immature lung. Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing were employed to comprehensively map the transcriptional landscapes of lung-resident cells. Marked differences in gene expression and cell-type distributions were observed between neonates and juveniles. Acute inflammatory responses in neonatal lungs were associated with decreased alveolar epithelial type 2 (AT2) cell proliferation, as well as a transient disruption of ligand-receptor interactions (Fgf1 and Fgfr4) between AT2 cells and secondary crest myofibroblasts. In contrast, juvenile immune and lung-resident cells were transcriptionally poised to respond to lung injury, dampening the acute inflammatory effects of E. coli on the lung. This study highlighted how early-life immune ontogeny impacts disease susceptibility, opening avenues for future research to identify therapeutic targets to enhance resistance to respiratory infections for the most vulnerable populations.