Osuna-Espinoza Kenia Y, Mejia-Torres Manuel G, Camacho-Ortiz Adrian, Perez-Alba Eduardo, Martinez-Castilla Azalia M, Salinas-Carmona Mario C, Rosas-Taraco Adrian G
Universidad Autónoma de Nuevo León, Servicio y Departamento de Inmunología, Facultad de Medicina, Monterrey, NL, Mexico.
Universidad Autónoma de Nuevo León, Servicio de Infectología, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González", Monterrey, NL, Mexico.
Front Cell Infect Microbiol. 2025 Aug 25;15:1636463. doi: 10.3389/fcimb.2025.1636463. eCollection 2025.
Natural killer (NK) cells are innate lymphocytes with cytotoxic activity against tumors and viruses. The pandemic of the coronavirus disease 2019 (COVID-19) has increased the investigation of their role in disease severity. However, their functional status and modulators remain controversial. Recent studies highlighted the role of metabolism in immune function, but metabolic changes in NK cells during SARS-CoV-2 infection remain unexplored. This study compares metabolic (, and ) and inflammatory (, and ) gene expression, and flow cytometry-based assessment of functional markers in NK cells from severe COVID-19 patients (n=15) and the control group (n=10), and their association with clinical outcomes. Severe COVID-19 patients exhibited elevated IFNγ, Granzyme B, and KIR2DL1 expression in NK cells compared to controls (), while LAMP1 was unchanged ( NK cells from deceased patients exhibited significantly lower expression levels of LAMP1 and Granzyme B (). Patients hospitalized >7 days presented lower Granzyme-B+ NK cells (). NK cells from severe COVID-19 patients showed downregulation of and , and upregulation of (). and expression were elevated in patients with >7 days of hospitalization (). SIRT1 expression was higher in patients requiring intubation (). , and were upregulated in deceased patients (). In conclusion, we demonstrate that NK cells from patients with severe COVID-19 exhibit increased functional markers and dysregulated metabolic gene expression associated with clinical outcomes.
自然杀伤（NK）细胞是一种先天性淋巴细胞，对肿瘤和病毒具有细胞毒性活性。2019年冠状病毒病（COVID-19）大流行增加了对其在疾病严重程度中作用的研究。然而，它们的功能状态和调节因子仍存在争议。最近的研究强调了代谢在免疫功能中的作用，但SARS-CoV-2感染期间NK细胞的代谢变化仍未得到探索。本研究比较了重症COVID-19患者（n = 15）和对照组（n = 10）NK细胞的代谢（、和）和炎症（、和）基因表达，以及基于流式细胞术的功能标志物评估，及其与临床结果的关联。与对照组相比，重症COVID-19患者NK细胞中的IFNγ、颗粒酶B和KIR2DL1表达升高（），而LAMP1无变化（死亡患者的NK细胞中LAMP1和颗粒酶B的表达水平显著降低（）。住院超过7天的患者中，颗粒酶B+NK细胞较少（）。重症COVID-19患者的NK细胞显示和下调，而上调（）。住院超过7天的患者中、和表达升高（）。需要插管的患者中SIRT1表达较高（）。死亡患者中、和上调（）。总之，我们证明重症COVID-19患者的NK细胞表现出与临床结果相关的功能标志物增加和代谢基因表达失调。
