Alveolar Macrophages Undergo a Postnatal Transition from a Hyperphagocytic and Proinflammatory Profile to a Tolerogenic Profile

While the ontogeny of AMs is well characterized, their postnatal phenotypic and functional maturation remains unclear. Here, we developed a bronchoalveolar lavage (BAL) protocol across key developmental stages and systematically analyzed age-dependent changes in AMs.

AM numbers increased with age, acquiring a mature phenotype alongside alveolar maturation.BAL-recovered AMs decreased in size and increased in roundness from day 3 onward and revealed distinct gene expression profiles across different ages. Functionally, phagocytic capacity peaked in 3-day-old mice. Furthermore, AMs from all ages beyond day 1 showed lower basal inflammatory cytokine expression and an attenuated response to LPS, indicating a postnatal transition toward a tolerant phenotype.