Neonates are highly susceptible to inflammation and infection. Here, we investigate how late fetal liver (FL) mouse hematopoietic stem and progenitor cells (HSPCs) respond to inflammation, testing the hypothesis that deficits in the engagement of emergency myelopoiesis (EM) pathways limit neutrophil output and contribute to perinatal neutropenia. We show that fetal HSPCs have limited production of myeloid cells at steady state and fail to activate a classical adult-like EM transcriptional program. Moreover, we find that fetal HSPCs can respond to EM-inducing inflammatory stimuli but are restricted by maternal anti-inflammatory factors, primarily interleukin-10 (IL-10), from activating EM pathways . Accordingly, we demonstrate that the loss of maternal IL-10 restores EM activation in fetal HSPCs but at the cost of fetal demise. These results reveal the evolutionary trade-off inherent in maternal anti-inflammatory responses that maintain pregnancy but render the fetus unresponsive to EM activation signals and susceptible to infection.

中文翻译：

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母体炎症调节胎儿紧急骨髓细胞生成

新生儿极易发生炎症和感染。在这里，我们研究了晚期胎肝 (FL) 小鼠造血干细胞和祖细胞 (HSPC) 对炎症的反应，检验了紧急骨髓生成 (EM) 途径参与缺陷限制中性粒细胞输出并导致围产期中性粒细胞减少症的假设。我们发现，胎儿 HSPC 在稳定状态下骨髓细胞的产生有限，并且无法激活经典的成人样 EM 转录程序。此外，我们发现胎儿 HSPC 可以对 EM 诱导的炎症刺激做出反应，但受到母体抗炎因子（主要是白细胞介素 10 (IL-10)）激活 EM 通路的限制。因此，我们证明母体 IL-10 的缺失可以恢复胎儿 HSPC 中的 EM 激活，但代价是胎儿死亡。这些结果揭示了母体抗炎反应中固有的进化权衡，这种反应可以维持妊娠，但使胎儿对电磁激活信号无反应，并且容易受到感染。