CC16 Deficiency in the Context of Early-Life Infection Results in Augmented Airway Responses in Adult Mice.

Studies have shown that club cell secretory protein (CC16) plays important protective roles in the lungs, yet its complete biological functions are unclear. We devised a translational mouse model in order to investigate the impact of early life infections, in the context of CC16 deficiency, on lung function in adult mice. CC16 sufficient (WT) and deficient (CC16) mice were infected with Mycoplasma pneumoniae (Mp) as weanlings and assessed as adults (arly ife nfection odel; ELIM) and compared to adult mice infected for only 3 days (dult nfection odel; AIM). CC16 Mp-infected mice had significantly increased airway hyperresponsiveness (AHR) in both models compared to WT mice. However, CC16 mice infected in early life (ELIM) displayed significantly increased AHR compared to CC16 mice infected in adulthood (AIM). In stark contrast, lung function in ELIM WT mice returned to levels similar to saline-treated controls. While WT mice cleared Mp infection in the ELIM, CC16 mice remained colonized with Mp throughout the model, which likely contributed to increased airway remodeling and persistence of expression. When CC16 mouse tracheal epithelial cells (MTECs) were infected with Mp, increased Mp colonization and collagen gene expression were also detected compared to WT cells, suggesting that CC16 plays a protective role during Mp infection, in part through epithelial-driven host defense mechanisms.