Neutrophils rapidly respond to inflammation and infection, but to which degree their functional trajectories after mobilization from the bone marrow are shaped within the circulation remains vague. Experimental limitations have so far hampered neutrophil research in human disease. Here, using innovative fixation and single-cell–based toolsets, we profile human and murine neutrophil transcriptomes and proteomes during steady state and bacterial infection. We find that peripheral priming of circulating neutrophils leads to dynamic shifts dominated by conserved up-regulation of antimicrobial genes across neutrophil substates, facilitating pathogen containment. We show the TLR4/NF-κB signaling–dependent up-regulation of canonical neutrophil activation markers like CD177/NB-1 during acute inflammation, resulting in functional shifts in vivo. Blocking de novo RNA synthesis in circulating neutrophils abrogates these plastic shifts and prevents the adaptation of antibacterial neutrophil programs by up-regulation of distinct effector molecules upon infection. These data underline transcriptional plasticity as a relevant mechanism of functional neutrophil reprogramming during acute infection to foster bacterial containment within the circulation.

中文翻译：

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外周启动诱导循环中性粒细胞的可塑性转录组和蛋白质组反应，这是遏制病原体所需的

中性粒细胞对炎症和感染迅速做出反应，但从骨髓动员后它们的功能轨迹在循环中形成的程度仍然模糊。迄今为止，实验的局限性阻碍了中性粒细胞在人类疾病中的研究。在这里，我们使用创新的固定和基于单细胞的工具集，对稳态和细菌感染期间的人类和小鼠中性粒细胞转录组和蛋白质组进行了分析。我们发现，循环中性粒细胞的外周启动导致动态变化，其主导因素是中性粒细胞亚状态中抗菌基因的保守上调，从而促进病原体的遏制。我们展示了急性炎症期间典型中性粒细胞激活标记物（如 CD177/NB-1）的 TLR4/NF-κB 信号依赖性上调，导致体内功能发生变化。阻断循环中性粒细胞中 RNA 从头合成可消除这些塑性转变，并通过感染时不同效应分子的上调来阻止抗菌中性粒细胞程序的适应。这些数据强调转录可塑性是急性感染期间功能性中性粒细胞重编程的相关机制，以促进循环内的细菌遏制。