Age-dependent immune responses and resident cell dynamics in young mice following pneumonia [RNA-Seq]

A developmental murine model of pneumonia was used to investigate how lower respiratory tract E. coli infections differentially affects lung immune responses and cell behavior in young mice (neonates; PND5 and juveniles; PND12). Acutely, juveniles recover more quickly than neonates, but alveolar simplification occurred in both groups 6-8 weeks post-infection. Single-cell RNA sequencing revealed transient inflammatory responses in neutrophils, macrophages, and fibroblasts at 48 h post infection in both age groups with a partial return to baseline by 96h. The highly proliferative neonatal alveolar type 2 (AT2) cells showed a modest decrease at 48h post infection, whereas the quiescent juvenile AT2 cells exhibited a proliferative response only post-infection. Neonatal PDGFRa+ fibroblasts had higher expression of inflammatory genes post infection than juveniles and in vitro stimulation of PDGFRa+ fibroblasts with LPS-exposed primary macrophages alone, induced expression of the inflammatory marker SAA3. We conclude that early-life pneumonia alters lung homeostasis in an age-differential manner, potentially affecting lung structure and function in adulthood. Overall design: Sorted AT2 cells or fibroblasts from the lungs of mice infected with E. coli or PBS (controls) at the neonatal (PND5) or juvenile (PND12) time-points were collected for bulk RNA-seq.