Expansion of myeloid-derived suppressor cells in patients with severe coronavirus disease (COVID-19)
Expansion of myeloid-derived suppressor cells in patients with severe coronavirus disease (COVID-19)
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DOI：
10.1038/s41418-020-0572-6
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发表时间：
2020-06-08
影响因子：
12.4
通讯作者：
Ippolito, Giuseppe
中科院分区：
文献类型：
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作者：
Agrati, Chiara;Sacchi, Alessandra;Ippolito, Giuseppe
SARS-CoV-2与严重疾病患者3.4%的死亡率相关。严重病例的发病机制尚不清楚。我们对两名严重COVID-19疾病患者从发病到康复期间的免疫和炎症标志物进行了深入的前瞻性分析。在入院时采集了18名SARS-CoV-2感染患者的外周血，其中9名为重度COVID-19疾病，9名为轻度COVID-19疾病，并分析了T细胞活化谱、髓源性抑制细胞（MDSC）和细胞因子谱。在体外测试MDSC功能。在四个严重的和在四个轻度患者，纵向分析进行了每天从入院到早期康复期。入院后早期，与轻度患者相比，重度患者表现出嗜中性粒细胞增多、淋巴细胞减少、效应T细胞增加、T细胞上CD 95的持续较高表达、较高的IL-6和TGF-β血清浓度以及NK和T细胞的细胞毒性特征，表明高度参与的免疫应答。观察到MDSC的大量扩增，在患有严重疾病的患者中高达总循环单核细胞的90%，在患有轻度疾病的患者中高达25%;频率随着恢复而降低。MDSC抑制T细胞功能，抑制过度的免疫反应。MDSC在恢复期的下降与血浆样品中TGF-β的减少和炎性细胞因子的增加有关。在严重COVID-19患者中观察到抑制细胞的大量扩增。需要进一步的研究来确定它们在减少过度活化/炎症、保护、影响疾病进展、作为疾病严重程度的生物标志物的潜力以及免疫和宿主导向治疗方法的新靶点方面的作用。
SARS-CoV-2 is associated with a 3.4% mortality rate in patients with severe disease. The pathogenesis of severe cases remains unknown. We performed an in-depth prospective analysis of immune and inflammation markers in two patients with severe COVID-19 disease from presentation to convalescence. Peripheral blood from 18 SARS-CoV-2-infected patients, 9 with severe and 9 with mild COVID-19 disease, was obtained at admission and analyzed for T-cell activation profile, myeloid-derived suppressor cells (MDSCs) and cytokine profiles. MDSC functionality was tested in vitro. In four severe and in four mild patients, a longitudinal analysis was performed daily from the day of admission to the early convalescent phase. Early after admission severe patients showed neutrophilia, lymphopenia, increase in effector T cells, a persisting higher expression of CD95 on T cells, higher serum concentration of IL-6 and TGF-beta, and a cytotoxic profile of NK and T cells compared with mild patients, suggesting a highly engaged immune response. Massive expansion of MDSCs was observed, up to 90% of total circulating mononuclear cells in patients with severe disease, and up to 25% in the patients with mild disease; the frequency decreasing with recovery. MDSCs suppressed T-cell functions, dampening excessive immune response. MDSCs decline at convalescent phase was associated to a reduction in TGF-beta and to an increase of inflammatory cytokines in plasma samples. Substantial expansion of suppressor cells is seen in patients with severe COVID-19. Further studies are required to define their roles in reducing the excessive activation/inflammation, protection, influencing disease progression, potential to serve as biomarkers of disease severity, and new targets for immune and host-directed therapeutic approaches.