Influenza-induced monocyte-derived alveolar macrophages confer prolonged antibacterial protection
Influenza-induced monocyte-derived alveolar macrophages confer prolonged antibacterial protection
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DOI：
10.1038/s41590-019-0568-x
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发表时间：
2020-01-13
影响因子：
30.5
通讯作者：
Wack, Andreas
中科院分区：
文献类型：
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作者：
Aegerter, Helena;Kulikauskaite, Justina;Wack, Andreas
呼吸道感染在整个生命过程中都会发生，但它如何随着时间的推移塑造肺部免疫系统尚不清楚。Wack和他的同事们发现，以前的流感感染将单核细胞募集到肺部，然后呈现肺泡巨噬细胞样表型并介导长期的抗菌保护。尽管流感流行且临床重要，但其对肺部免疫的长期影响尚不清楚。在这里，我们描述了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）产生增加的白细胞介素-6（IL-6），小鼠更好地保护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，流感经验的居民AM仍然在很大程度上类似于初治AM。因此，流感改变了AM群体的组成，以提供长期的抗菌保护。单核细胞衍生的AM随着时间的推移而持续存在，但失去了它们的保护作用。我们的研究结果有助于了解短暂性呼吸道感染（人类生活中常见的疾病）如何通过向AM群体提供单核细胞衍生的招募细胞来不断改变肺部免疫力。
Respiratory infections occur throughout life but how this shapes the lung immune system through time is unclear. Wack and colleagues show that a previous influenza infection recruits monocytes to the lung, which then assume an alveolar macrophage-like phenotype and mediate long-term antibacterial protection.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.