Tissue-resident macrophages (MΦTR ) originate from at least two distinct waves of erythro-myeloid progenitors (EMP) arising in the yolk sac (YS) at E7.5 and E8.5 with the latter going through a liver monocyte intermediate. The relative potential of these precursors in determining development and functional capacity of MΦTR remains unclear. Here, we studied development of alveolar macrophages (AM) after single and competitive transplantation of different precursors from YS, fetal liver, and fetal lung into neonatal Csf2ra-/- mice, which lack endogenous AM. Fetal monocytes, promoted by Myb, outcompeted primitive MΦ (pMΦ) in empty AM niches and preferentially developed to mature AM, which is associated with enhanced mitochondrial respiratory and glycolytic capacity and repression of the transcription factors c-Maf and MafB. Interestingly, AM derived from pMΦ failed to efficiently clear alveolar proteinosis and protect from fatal lung failure following influenza virus infection. Thus, our data demonstrate superior developmental and functional capacity of fetal monocytes over pMΦ in AM development and underlying mechanisms explaining replacement of pMΦ in fetal tissues.

中文翻译：

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胎儿单核细胞具有增加的代谢能力，并取代组织巨噬细胞发育中的原始巨噬细胞。

组织驻留巨噬细胞（MΦTR）源自卵黄囊（YS）在E7.5和E8.5处产生的至少两个不同的红系髓系祖细胞（EMP）波，后者通过肝单核细胞中间体。这些前体在确定MΦTR的发育和功能能力方面的相对潜力尚不清楚。在这里，我们研究了将来自YS，胎儿肝脏和胎儿肺的不同前体单次竞争性移植到缺乏内源性AM的新生Csf2ra-/-小鼠中后肺泡巨噬细胞（AM）的发育。由Myb促进的胎儿单核细胞在空空的AM区域中胜过原始MΦ（pMΦ），并优先发展为成熟的AM，这与增强的线粒体呼吸和糖酵解能力以及转录因子c-Maf和MafB的抑制有关。有趣的是，源自pMΦ的AM无法有效清除肺泡蛋白沉着症，并无法防止流感病毒感染后致命的肺衰竭。因此，我们的数据表明，在AM发育中，胎儿单核细胞的发育和功能能力优于pMΦ，其基本机制解释了胎儿组织中pMΦ的替代。