Infants are more likely to develop lethal disseminated forms of tuberculosis compared with older children and adults. The reasons for this are currently unknown. In this study we test the hypothesis that antimycobacterial function is impaired in infant alveolar macrophages (AMϕs) compared with those of adults. We develop a method of obtaining AMϕs from healthy infants using rigid bronchoscopy and incubate the AMϕs with live virulent Mycobacterium tuberculosis (Mtb). Infant AMϕs are less able to restrict Mtb replication compared with adult AMϕs, despite having similar phagocytic capacity and immunophenotype. RNA-Seq showed that infant AMϕs exhibit lower expression of genes involved in mycobactericidal activity and IFNγ-induction pathways. Infant AMϕs also exhibit lower expression of genes encoding mononuclear cell chemokines such as CXCL9. Our data indicates that failure of AMϕs to contain Mtb and recruit additional mononuclear cells to the site of infection helps to explain the more fulminant course of tuberculosis in early life.

中文翻译：

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婴儿肺泡巨噬细胞无法有效遏制结核分枝杆菌。


与年龄较大的儿童和成人相比，婴儿更有可能患上致命的播散性结核病。目前尚不清楚其原因。在这项研究中，我们检验了以下假设：与成人相比，婴儿肺泡巨噬细胞 (AMphis) 的抗分枝杆菌功能受损。我们开发了一种使用硬质支气管镜从健康婴儿获取 AMφs 的方法，并将 AMφs 与活毒力结核分枝杆菌 (Mtb) 一起孵育。尽管具有相似的吞噬能力和免疫表型，但与成人 AMΦs 相比，婴儿 AMΦs 限制 Mtb 复制的能力较差。 RNA-Seq 显示，婴儿 AMphi 中参与分枝杆菌活性和 IFNγ 诱导途径的基因表达较低。婴儿 AMphis 还表现出编码单核细胞趋化因子（例如 CXCL9）的基因表达较低。我们的数据表明，AMphis 未能抑制 Mtb 并招募额外的单核细胞到感染部位，这有助于解释生命早期结核病的暴发性病程。