Sepsis is a common serious clinical infectious disease accompanied by more severe injuries and higher mortality rates in men than women. The much higher level of 17β-estradiol (E₂) in female is one of the significant reasons for better sepsis resistance ability. Trained immunity is a novel way to fight against infection by improving innate immunity. However, whether β-glucan-induced trained immunity can promote macrophage phagocytosis to clear infections in early sepsis has not been clarified. And whether E₂ involved in this process needs further investigation. Symptoms among male, female and ovariectomized (OVX) C57BL/6 mice in early sepsis were detected. The effect of trained immunity on macrophage LC3B-associated phagocytosis (LAP) and the mechanism of E₂ functioned in this process have also been explored. We demonstrated compared with male mice, female has significantly more mild symptoms and more reactive oxygen species (ROS) production and stronger NADPH oxidase 2 (NOX2) expression in the macrophage of major organs. In contrary, these characteristics are disappeared in OVX mice. Furthermore, in macrophage cell lines and primary bone marrow- derived macrophages (BMDMs), β-glucan-induced trained immunity can increase ROS production by activating NOX2 to promote macrophage LAP. E₂ can up-regulate RUBICON through estrogen receptor α (ERα) to further facilitate macrophage LAP. These results indicated that trained immunity can improve sepsis resistance ability by stimulating macrophage LAP. E₂ can boost ROS production and RUBICON expression to further promote macrophage LAP, which can provide a new perspective to recognize the mechanism of trained immunity in gender differences when responding to sepsis.

中文翻译：

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17β-雌二醇在雌性小鼠对败血症的训练免疫中促进 LC3B 相关的吞噬作用

脓毒症是一种常见的严重临床传染病，男性比女性受伤更严重，死亡率更高。女性体内较高水平的 17β-雌二醇 (E ₂ ) 是抗败血症能力更好的重要原因之一。训练有素的免疫力是一种通过提高先天免疫力来对抗感染的新方法。然而，β-葡聚糖诱导的训练性免疫是否能促进巨噬细胞吞噬作用以清除脓毒症早期感染尚不清楚。而E ₂是否参与这个过程还需要进一步调查。检测到早期败血症的雄性、雌性和去卵巢 (OVX) C57BL/6 小鼠的症状。训练免疫对巨噬细胞 LC3B 相关吞噬作用 (LAP) 的影响及 E _{2的作用机制}在这个过程中发挥作用的也进行了探索。我们证明，与雄性小鼠相比，雌性小鼠的主要器官巨噬细胞中的症状明显更轻，活性氧 (ROS) 产生更多，NADPH 氧化酶 2 (NOX2) 表达更强。相反，这些特征在 OVX 小鼠中消失了。此外，在巨噬细胞系和原代骨髓衍生巨噬细胞 (BMDM) 中，β-葡聚糖诱导的训练免疫可以通过激活 NOX2 来促进巨噬细胞 LAP 来增加 ROS 的产生。E ₂可通过雌激素受体α（ERα）上调RUBICON，进一步促进巨噬细胞LAP。这些结果表明，经过训练的免疫可以通过刺激巨噬细胞 LAP 来提高抗败血症的能力。E ₂ 可促进 ROS 产生和 RUBICON 表达以进一步促进巨噬细胞 LAP，这可以提供一个新的视角来认识在应对脓毒症时训练的免疫在性别差异中的机制。