Bronchopulmonary dysplasia (BPD) is a frequent and severe complication of very premature infants that is associated with life-long consequences.  Therapies to effectively prevent and treat BPD are scarce, due to a lack of clinically relevant preclinical models simulating the multifactorial pathogenesis of BPD. This project establishes a novel two-hit preclinical model of prenatal infection and postnatal oxygen exposure mimicking the most frequent clinical scenarios experienced by preterm infants. The ultimate aim is to identify novel therapeutic targets to hinder BPD development, with focus on the crosstalk between macrophages and mesenchymal cells which are key orchestrators of lung injury. In parallel, preclinical results will be validated using clinical biosamples.