Neutrophil clean-up in experimental acute sterile lung injury: de novo DNA degradation leads to lung repair. Bone marrow–derived neutrophils (BM neutrophils) lack the ability to degrade DNA-containing debris. However, alveolar neutrophils acquire this ability following exposure to an inflammatory milieu. Oved et al demonstrate that sterile acute lung injury following acid inhalation induces de novo expression of DNA-sensing DAMP receptors, MyD88-dependent transcription, and protein synthesis of DNA-degradative factors (TREX1, WRN, DNASE1L3), leading to clearance of DNA-containing debris that otherwise hinders lung recovery. Neutropenic mice do not clear DNA-containing lung debris in this model, leading to failed lung repair, but tracheal treatment with DNase I rescues the lung repair phenotype.