Staphylococcus epidermidis Sensitizes Perinatal Hypoxic-Ischemic Brain Injury in Male but Not Female Mice
Staphylococcus epidermidis Sensitizes Perinatal Hypoxic-Ischemic Brain Injury in Male but Not Female Mice
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DOI：
10.3389/fimmu.2020.00516
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发表时间：
2020-04-21
影响因子：
7.3
通讯作者：
Lai, Jacqueline C. Y.
中科院分区：
文献类型：
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作者：
Gravina, Giacomo;Svedin, Pernilla;Lai, Jacqueline C. Y.
背景：表皮葡萄球菌是最常见的医院感染，也是早产儿迟发性脓毒症的主要病原体。感染和炎症与神经和发育后遗症有关，细菌感染增加了大脑对缺氧缺血（HI）的脆弱性。因此，我们检验了S.方法：雄性和雌性C57 B1/6小鼠腹腔注射无菌盐水或3.5 × 10（7）菌落形成单位的S.于出生后第4天（PND）处死小鼠，然后于PND 5（注射后24 h）或PND 9（注射后5 d）通过结扎左颈动脉和暴露于10% O-2进行HI。在PND 14 -16评估了白色和灰质损伤。在另一组动物中，在感染后PND 5或PND 9收集血浆、脑和肝脏以评估细胞因子和趋化因子谱、C5 a水平和C5信号传导。与盐水注射对照组相比，在雄性动物中，表皮注射导致更大的灰色和白色物质损伤，但在雌性动物中没有。具体而言，雄性动物表现出皮质和纹状体中灰质损伤增加，皮质下区域、海马伞和纹状体中白色物质丢失。与此相反，有没有增强脑损伤时，HI感染后5天发生在任何性别。在等离子体中，S.注射表皮炎的小鼠在感染后24小时表现出促炎和抗炎细胞因子和趋化因子水平的增加以及C5 a的减少，但在感染后5天没有。感染后24 h，两种性别的脑CCL 2水平均升高，但仅在感染后5 d，雄性脑CCL 2水平升高。表皮感染与新生儿HI的结合增加了雄性小鼠发育中大脑的脆弱性，但在雌性小鼠中没有。这些性别依赖性效应在很大程度上独立于全身性细胞因子或脑CCL 2表达的表达。总体而言，我们为系统性S. Epidermidis感染影响发育中的大脑，并表明感染和HI之间的时间间隔是男性的关键致敏因素。
Background: Staphylococcus epidermidis is the most common nosocomial infection and the predominant pathogen in late-onset sepsis in preterm infants. Infection and inflammation are linked to neurological and developmental sequelae and bacterial infections increase the vulnerability of the brain to hypoxia-ischemia (HI). We thus tested the hypothesis that S. epidermidis exacerbates HI neuropathology in neonatal mice.Methods: Male and female C57Bl/6 mice were injected intraperitoneally with sterile saline or 3.5 x 10(7) colony-forming units of S. epidermidis on postnatal day (PND) 4 and then subjected to HI on PND5 (24 h after injection) or PND9 (5 d after injection) by left carotid artery ligation and exposure to 10% O-2. White and gray matter injury was assessed on PND14-16. In an additional group of animals, the plasma, brain, and liver were collected on PND5 or PND9 after infection to evaluate cytokine and chemokine profiles, C5a levels and C5 signaling.Results: HI induced 24 h after injection of S. epidermidis resulted in greater gray and white matter injury compared to saline injected controls in males, but not in females. Specifically, males demonstrated increased gray matter injury in the cortex and striatum, and white matter loss in the subcortical region, hippocampal fimbria and striatum. In contrast, there was no potentiation of brain injury when HI occurred 5 d after infection in either sex. In the plasma, S. epidermidis-injected mice demonstrated increased levels of pro- and anti-inflammatory cytokines and chemokines and a reduction of C5a at 24 h, but not 5 d after infection. Brain CCL2 levels were increased in both sexes 24 h after infection, but increased only in males at 5 d post infection.Conclusion: Ongoing S. epidermidis infection combined with neonatal HI increases the vulnerability of the developing brain in male but not in female mice. These sex-dependent effects were to a large extent independent of expression of systemic cytokines or brain CCL2 expression. Overall, we provide new insights into how systemic S. epidermidis infection affects the developing brain and show that the time interval between infection and HI is a critical sensitizing factor in males.