CD151 identifies an NK cell subset that is enriched in COVID-19 patients and correlates with disease severity

IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Journal of Infection Pub Date : 2024-10-05 DOI:10.1016/j.jinf.2024.106304
Ainhoa Amarilla-Irusta , Olatz Zenarruzabeitia , Arrate Sevilla , Víctor Sandá , Ainara Lopez-Pardo , Gabirel Astarloa-Pando , Raquel Pérez-Garay , Silvia Pérez-Fernández , Susana Meijide , Natale Imaz-Ayo , Eunate Arana-Arri , Laura Amo , Francisco Borrego
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Abstract

Severe coronavirus disease 2019 (COVID-19) often leads to acute respiratory distress syndrome and multi-organ dysfunction, driven by a dysregulated immune response, including a cytokine storm with elevated proinflammatory cytokine levels. Natural killer (NK) cells are part of the innate immune system with a fundamental role in the defense against viral infections. However, during COVID-19 acute infection, they exhibit an altered phenotype and impaired functionality contributing to the immunopathogenesis of the disease. In this work, we have studied a cohort of patients with COVID-19 (ranging from mild to severe) by analyzing IL-15, TGF-β, PlGF and GDF-15 plasma levels and performing multiparametric flow cytometry studies. Our results revealed that severe COVID-19 patients exhibited high levels of IL-15, PlGF and GDF-15, along with an enrichment of an NK cell subset expressing the CD151 tetraspanin, which correlated with IL-15 plasma levels and disease severity. In patients, these CD151+ NK cells displayed a more activated phenotype characterized by an increased expression of HLA-DR, CD38 and granzyme B, a distinct receptor repertoire, with lower levels of CD160 and CD31 and higher levels of CD55 and, remarkably, a higher expression of tissue-resident markers CD103 and the NK cell decidual marker CD9. Last of all, in individuals with severe disease, we identified an expansion of a CD151brightCD9+ NK cell subset, suggesting that these cells play a specific role in COVID-19. Altogether, our findings suggest that CD151+ NK cells may have a relevant role in COVID-19 immunopathogenesis.
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CD151 确定了一个 NK 细胞亚群,该亚群在 COVID-19 患者中富集,并与疾病严重程度相关。
严重的冠状病毒病2019年最新注册送彩金(COVID-19)通常会导致急性呼吸窘迫综合征和多器官功能障碍,其驱动因素是失调的免疫反应,包括细胞因子风暴和促炎细胞因子水平升高。自然杀伤(NK)细胞是先天性免疫系统的一部分,在抵御病毒感染方面发挥着重要作用。然而,在 COVID-19 急性感染期间,它们会表现出表型改变和功能受损,从而导致疾病的免疫发病机制。在这项工作中,我们通过分析 IL-15、TGF-β、PlGF 和 GDF-15 的血浆水平以及进行多参数流式细胞术研究,对 COVID-19 患者(从轻度到重度不等)进行了研究。我们的研究结果表明,COVID-19 重症患者的 IL-15、PlGF 和 GDF-15 水平较高,表达 CD151 四聚体蛋白的 NK 细胞亚群也较丰富,这与 IL-15 血浆水平和疾病严重程度相关。在患者体内,这些 CD151+ NK 细胞显示出更活化的表型,其特点是 HLA-DR、CD38 和颗粒酶 B 的表达增加,受体谱系独特,CD160 和 CD31 水平较低,CD55 水平较高,而且值得注意的是,组织驻留标记 CD103 和 NK 细胞蜕膜标记 CD9 的表达较高。最后,在病情严重的个体中,我们发现了 CD151brightCD9+ NK 细胞亚群的扩增,这表明这些细胞在 COVID-19 中发挥着特殊作用。总之,我们的研究结果表明,CD151+ NK 细胞可能在 COVID-19 免疫发病机制中发挥了相关作用。
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来源期刊
Journal of Infection
Journal of Infection 医学-传染病学
CiteScore
45.90
自引率
3.20%
发文量
475
审稿时长
16 days
期刊介绍: The Journal of Infection publishes original papers on all aspects of infection - clinical, microbiological and epidemiological. The Journal seeks to bring together knowledge from all specialties involved in infection research and clinical practice, and present the best work in the ever-changing field of infection. Each issue brings you Editorials that describe current or controversial topics of interest, high quality Reviews to keep you in touch with the latest developments in specific fields of interest, an Epidemiology section reporting studies in the hospital and the general community, and a lively correspondence section.
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