AbstractIntroductionStroke‐associated pneumonia (SAP) is a major cause of mortality in patients who have suffered from severe ischemic stroke. Although multifactorial in nature, stroke‐induced immunosuppression plays a key role in the development of SAP. Previous studies using a murine model of transient middle cerebral artery occlusion (tMCAO) have shown that focal ischemic stroke induction results in functional defects of lymphocytes in the spleen, thymus, and peripheral blood, leading to spontaneous bacterial infection in the lungs without inoculation. However, how ischemic stroke alters immune cell niche and the expression of cytokines and chemokines in the lungs has not been fully characterized.MethodsIschemic stroke was induced in mice by tMCAO. Immune cell profiles in the brain and the lungs at 24‐ and 72‐hour time points were compared by flow cytometric analysis. Cytokine and chemokine expression in the lungs were determined by multiplex bead arrays. Tissue damage and bacterial burden in the lungs following tMCAO were evaluated.ResultsIschemic stroke increases the percentage of alveolar macrophages, neutrophils, and CD11b+ dendritic cells, but reduces the percentage of CD4+ T cells, CD8+ T cells, B cells, natural killer cells, and eosinophils in the lungs. The alteration of immune cell niche in the lungs coincides with a significant reduction in the levels of multiple chemokines in the lungs, including CCL3, CCL4, CCL5, CCL17, CCL20, CCL22, CXCL5, CXCL9, and CXCL10. Spontaneous bacterial infection and tissue damage following tMCAO, however, were not observed.ConclusionThis is the first report to demonstrate a significant reduction of lymphocytes and multiple proinflammatory chemokines in the lungs following ischemic stroke in mice. These findings suggest that ischemic stroke directly impacts pulmonary immunity.

中文翻译：

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缺血性中风改变小鼠的免疫细胞生态位和趋化因子谱，与自发细菌感染无关

摘要介绍中风相关性肺炎（SAP）是严重缺血性中风患者死亡的主要原因。尽管本质上是多因素的，但中风引起的免疫抑制在 SAP 的发展中起着关键作用。先前使用短暂性大脑中动脉闭塞（tMCAO）小鼠模型的研究表明，局灶性缺血性中风诱导会导致脾脏、胸腺和外周血中淋巴细胞的功能缺陷，导致未经接种的肺部自发细菌感染。然而，缺血性中风如何改变免疫细胞生态位以及肺部细胞因子和趋化因子的表达尚未得到充分表征。方法tMCAO 在小鼠中诱导缺血性中风。通过流式细胞术分析比较 24 小时和 72 小时时间点大脑和肺部的免疫细胞谱。通过多重珠阵列测定肺中细胞因子和趋化因子的表达。评估了 tMCAO 后肺部的组织损伤和细菌负荷。结果缺血性中风增加肺泡巨噬细胞、中性粒细胞和 CD11b 的百分比+树突状细胞，但降低了 CD4 的百分比+T细胞，CD8+肺部的 T 细胞、B 细胞、自然杀伤细胞和嗜酸性粒细胞。肺部免疫细胞生态位的改变与肺部多种趋化因子水平的显着降低相一致，包括CCL3、CCL4、CCL5、CCL17、CCL20、CCL22、CXCL5、CXCL9和CXCL10。然而，没有观察到 tMCAO 后的自发细菌感染和组织损伤。结论这是第一份证明小鼠缺血性中风后肺部淋巴细胞和多种促炎趋化因子显着减少的报告。这些发现表明缺血性中风直接影响肺部免疫力。