暴露于雄激素会影响中性粒细胞的成熟和感染脏中的功能
Teri N Hreha1, Christina A Collins1, Elisabeth B Cole1
1Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
mBio
|January 11, 2024
概括
暴露于雌激素会损害尿路中中性粒细胞的成熟和功能,增加小鼠对严重尿路感染 (UTI) 和损伤的易感性. 这就解释了为什么男性可能会出现更糟糕的尿路感染结果.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 泌尿器科 泌尿器科 泌尿器科 泌尿器科
背景情况:
- 尿路感染 (UTI) 在男性中不太常见,但会导致更严重的结果,如肺炎炎.
- 众所周知,像丸激素一样,雄激素会影响尿路感染的严重程度,但潜在的机制尚不清楚.
- 之前的研究表明,在C3H/HeN小鼠中,有高细菌标位和的素依赖性肺炎.
研究的目的:
- 调查雄激素如何影响在尿路感染 (UTI) 期间的中性粒细胞功能和成熟.
- 阐明雄激素增加易患重症肺炎和脏的机制.
- 为了确定在尿路感染病变发生过程中,雄激素受体信号传递在髓状细胞中的作用.
主要方法:
- 雌性C3H小鼠暴露于雄激素,并感染尿病原性大肠杆菌 (UPEC).
- 在脏,脏,骨髓和膀中评估了中性粒细胞的成熟和功能,使用流细胞计和体外测试.
- 有条件的雄激素受体 (AR) 缺乏的小鼠 (B6背景) 与髓状细胞特异性AR删除被用于评估AR信号.
- 在感染脏中测量了促炎性细胞因子反应和细菌负载.
主要成果:
- 对雄激素的暴露导致了局部炎症反应的延迟和感染脏中强大的中性粒细胞招募.
- 暴露于雄激素的小鼠中的脏中性粒细胞已老化,不成熟 (CD49d+,CD101-),并且表现出减少的细胞和脱粒功能.
- 中性粒细胞功能障碍是特定于脏的,脏,骨髓和膀中性粒细胞不受影响.
- 骨髓细胞中受体的删除挽救了中性粒细胞成熟缺陷.
- 暴露于雄激素的小鼠表现出持续的高位感染和形成的增加.
结论:
- 在UPEC感染期间,雄激素会损害尿路中核细胞的成熟和功能,特别是在脏中.
- 这种中性粒细胞抗微生物能力的局部损害,由细胞内在的AR信号传递介导,有助于增加胰腺炎的严重程度和雄激素暴露个体的炎症.
- 这些发现突出了一个关键机制,解释了男性患严重尿路感染和并发症的风险更高.
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