Despite the prevalence and clinical importance of influenza, its long-term effect on lung immunity is unclear. Here we describe that following viral clearance and clinical recovery, at 1 month after infection with influenza, mice are better protected from Streptococcus pneumoniae infection due to a population of monocyte-derived alveolar macrophages (AMs) that produce increased interleukin-6. Influenza-induced monocyte-derived AMs have a surface phenotype similar to resident AMs but display a unique functional, transcriptional and epigenetic profile that is distinct from resident AMs. In contrast, influenza-experienced resident AMs remain largely similar to naive AMs. Thus, influenza changes the composition of the AM population to provide prolonged antibacterial protection. Monocyte-derived AMs persist over time but lose their protective profile. Our results help to understand how transient respiratory infections, a common occurrence in human life, can constantly alter lung immunity by contributing monocyte-derived, recruited cells to the AM population.

尽管流感很流行且具有临床重要性，但其对肺部免疫的长期影响尚不清楚。在这里，我们描述了在病毒清除和临床恢复后，在感染流感后 1 个月，由于单核细胞来源的肺泡巨噬细胞 (AM) 群体产生增加的白细胞介素 6，小鼠可以更好地免受肺炎链球菌感染。流感诱导的单核细胞来源的 AM 具有与常驻 AM 相似的表面表型，但显示出与常驻 AM 不同的独特功能、转录和表观遗传特征。相比之下，经历过流感的常驻 AM 与未接触过流感的 AM 基本相似。因此，流感改变了 AM 群体的组成，以提供长期的抗菌保护。单核细胞来源的 AM 会随着时间的推移而持续存在，但会失去其保护作用。我们的研究结果有助于了解人类生活中常见的短暂性呼吸道感染如何通过将单核细胞来源的招募细胞贡献给 AM 群体来不断改变肺部免疫力。