肠道菌群缺乏可减少中性粒细胞活化,并在缺血性中风后起到保护作用。

IF 10.1 1区 医学 Q1 IMMUNOLOGY
Ali A Tuz, Susmita Ghosh, Laura Karsch, Medina Antler, Vivian Lakovic, Sabrina Lohmann, Amber Hope Lehmann, Alexander Beer, Dennis Nagel, Marcel Jung, Nils Hörenbaum, Viola Kaygusuz, Altea Qefalia, Belal Alshaar, Niloufar Amookazemi, Silvia Bolsega, Marijana Basic, Jens T Siveke, Sven Heiles, Anika Grüneboom, Smiths Lueong, Josephine Herz, Albert Sickmann, Nina Hagemann, Anja Hasenberg, Dirk M Hermann, Matthias Gunzer, Vikramjeet Singh
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引用次数: 0

摘要

中性粒细胞是小鼠和患者缺血性中风后容易激活的免疫细胞。尽管如此,肠道微生物群对中性粒细胞活化的影响及其对炎症性脑损伤的影响仍未明确。我们报道,无菌(GF)小鼠的自然微生物群定植诱导大量中性粒细胞活化并恶化中风病理。定植的前GF中风小鼠的梗死面积和感觉运动缺陷明显大于GF同窝小鼠。此外,采用基于抗生素的微生物群缺乏小鼠模型,我们证明肠道微生物群消耗诱导幼中性粒细胞表型,其特征是静息状态表面受体上调,炎症蛋白减少和循环NETs水平降低。中性粒细胞反应的解除与脑炎症基因表达减少、血管血栓形成、梗死面积减小和行为缺陷减轻有关。我们得出结论,肠道微生物强烈影响中风后中性粒细胞的激活,从而直接影响中风的严重程度。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Gut microbiota deficiency reduces neutrophil activation and is protective after ischemic stroke.

Neutrophils are readily activated immune cells after ischemic stroke in mice and patients. Still, the impact of gut microbiota on neutrophil activation and its influence on inflammatory brain injury remain undefined. We report that natural microbiota colonization of germ-free (GF) mice induces substantial neutrophil activation and deteriorates stroke pathology. The colonized Ex-GF stroke mice had considerably larger infarct sizes and higher sensorimotor deficits than GF littermates. Furthermore, employing an antibiotic-based mouse model of microbiota deficiency, we demonstrate that gut microbiota depletion induces a juvenile neutrophil phenotype characterized by the upregulation of resting state surface receptors, reduced inflammatory proteins, and levels of circulating NETs. This disarming of neutrophil responses was associated with decreased expression of brain inflammatory genes, vascular thrombus formation, reduced infarct size, and alleviated behavioral deficits. We conclude that gut microbes strongly influence neutrophil activation after stroke and thus directly contribute to stroke severity.

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来源期刊
Journal of Neuroinflammation
Journal of Neuroinflammation 医学-神经科学
CiteScore
15.90
自引率
3.20%
发文量
276
审稿时长
1 months
期刊介绍: The Journal of Neuroinflammation is a peer-reviewed, open access publication that emphasizes the interaction between the immune system, particularly the innate immune system, and the nervous system. It covers various aspects, including the involvement of CNS immune mediators like microglia and astrocytes, the cytokines and chemokines they produce, and the influence of peripheral neuro-immune interactions, T cells, monocytes, complement proteins, acute phase proteins, oxidative injury, and related molecular processes. Neuroinflammation is a rapidly expanding field that has significantly enhanced our knowledge of chronic neurological diseases. It attracts researchers from diverse disciplines such as pathology, biochemistry, molecular biology, genetics, clinical medicine, and epidemiology. Substantial contributions to this field have been made through studies involving populations, patients, postmortem tissues, animal models, and in vitro systems. The Journal of Neuroinflammation consolidates research that centers around common pathogenic processes. It serves as a platform for integrative reviews and commentaries in this field.
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