Interstitial Macrophages Mediate Efferocytosis of Alveolar Epithelium during Influenza Infection.
Interstitial Macrophages Mediate Efferocytosis of Alveolar Epithelium during Influenza Infection.
复制标题
流感感染期间间质巨噬细胞介导肺泡上皮的胞吞作用。
DOI：
10.1165/rcmb.2023-0217ma
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发表时间：
2024
影响因子：
6.4
通讯作者：
Chen,Peter
中科院分区：
文献类型：
--
作者：
Zuttion,MariliaSanchezSantosRizzo;Parimon,Tanyalak;Yao,Changfu;Stripp,BarryR;Wang,Ying;Soto,ChristopherM;Ortega,Zackary;Li,Xiao;Janssen,WilliamJ;Chen,Peter
效应细胞增多症是通过清除凋亡细胞来维持组织内环境平衡的过程。在肺部，胞吐与几种急慢性炎症性疾病有关。一种长期存在的研究细胞吞噬素活体的方法是将凋亡细胞注入肺内，以评估巨噬细胞的摄取。然而，这种方法将非生理性水平的细胞提供给空气，在那里有优先进入肺泡巨噬细胞的途径。为了克服这一局限性，我们开发了一种新的方法来研究体内受损的肺泡2型(AT2)上皮细胞的胞吐作用。用流感病毒株(PR8株)损伤AT2上皮细胞表达TdTomato的小鼠，诱导AT2细胞凋亡。我们能够识别出在流感损伤后获得红色荧光的巨噬细胞，这表明AT2细胞有吞噬作用。此外，对巨噬细胞种群的评估导致了令人惊讶的发现，肺间质巨噬细胞是活着的主要外膜细胞蛋白。综上所述，我们提出了一个新的发现，即在流感感染后，间质巨噬细胞而不是肺泡巨噬细胞主要介导AT2细胞在肺部的清除。我们研究胞吐作用的方法为评估体内凋亡细胞清除的时空动力学提供了一种更生理学的方法，并为研究胞泡吞噬调节炎症的机制开辟了新的途径。
Efferocytosis is a process whereby apoptotic cells are cleared to maintain tissue homeostasis. In the lungs, efferocytosis has been implicated in several acute and chronic inflammatory diseases. A long-standing method to study efferocytosisin vivois to instill apoptotic cells into the lungs to evaluate macrophage uptake. However, this approach provides nonphysiologic levels of cells to the airspaces, where there is preferential access to the alveolar macrophages. To circumvent this limitation, we developed a new method to study efferocytosis of damaged alveolar type 2 (AT2) epithelial cellsin vivo. A reporter mouse that expresses TdTomato in AT2 epithelial cells was injured with influenza (strain PR8) to induce apoptosis of AT2 cells. We were able to identify macrophages that acquire red fluorescence after influenza injury, indicating efferocytosis of AT2 cells. Furthermore, evaluation of macrophage populations led to the surprising finding that lung interstitial macrophages were the primary efferocytein vivo.In summary, we present a novel finding that the interstitial macrophage, not the alveolar macrophage, primarily mediates clearance of AT2 cells in the lungs after influenza infection. Our method of studying efferocytosis provides a more physiologic approach in evaluating the spatiotemporal dynamics of apoptotic cell clearancein vivoand opens new avenues to study the mechanisms by which efferocytosis regulates inflammation.