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哥伦比亚 Sars-CoV-2 感染家系的免疫特征

Immune characterization of a Colombian family cluster with SARS-CoV-2 infection.

机构信息

Grupo de Inmunovirología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.

Grupo de Inmunovirología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia; Grupo de Salud y Comunidad, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.

出版信息

Biomedica. 2021 Oct 15;41(Sp. 2):86-102. doi: 10.7705/biomedica.5976.

Abstract

INTRODUCTION

Immunological markers have been described during COVID-19 and persist after recovery. These immune markers are associated with clinical features among SARSCoV-2 infected individuals. Nevertheless, studies reporting a comprehensive analysis of the immune changes occurring during SARS-CoV-2 infection are still limited.

OBJECTIVE

To evaluate the production of proinflammatory cytokines, the antibody response, and the phenotype and function of NK cells and T cells in a Colombian family cluster with SARS-CoV-2 infection.

MATERIALS AND METHODS

Proinflammatory cytokines were evaluated by RT-PCR and ELISA. The frequency, phenotype, and function of NK cells (cocultures with K562 cells) and T-cells (stimulated with spike/RdRp peptides) were assessed by flow cytometry. Anti-SARS-CoV-2 antibodies were determined using indirect immunofluorescence and plaque reduction neutralization assay.

RESULTS

During COVID-19, we observed a high proinflammatory-cytokine production and a reduced CD56bright-NK cell and cytotoxic response. Compared with healthy controls, infected individuals had a higher frequency of dysfunctional CD8+ T cells CD38+HLA-DR-. During the acute phase, CD8+ T cells stimulated with viral peptides exhibited a monofunctional response characterized by high IL-10 production. However, during recovery, we observed a bifunctional response characterized by the co-expression of CD107a and granzyme B or perforin.

CONCLUSION

Although the proinflammatory response is a hallmark of SARS-CoV-2 infection, other phenotypic and functional alterations in NK cells and CD8+ T cells could be associated with the outcome of COVID-19. However, additional studies are required to understand these alterations and to guide future immunotherapy strategies.

摘要

简介

在 COVID-19 期间已经描述了免疫标志物,并且在恢复后仍然存在。这些免疫标志物与 SARSCoV-2 感染个体的临床特征相关。然而,报告 SARS-CoV-2 感染期间发生的全面免疫变化的研究仍然有限。

目的

评估哥伦比亚 SARS-CoV-2 感染家族群中促炎细胞因子的产生、抗体反应以及 NK 细胞和 T 细胞的表型和功能。

材料和方法

通过 RT-PCR 和 ELISA 评估促炎细胞因子。通过流式细胞术评估 NK 细胞(与 K562 细胞共培养)和 T 细胞(用刺突/RdRp 肽刺激)的频率、表型和功能。使用间接免疫荧光法和蚀斑减少中和试验测定抗 SARS-CoV-2 抗体。

结果

在 COVID-19 期间,我们观察到高促炎细胞因子产生和 CD56bright-NK 细胞和细胞毒性反应降低。与健康对照相比,感染个体具有更高频率的功能失调 CD8+T 细胞 CD38+HLA-DR-。在急性期,用病毒肽刺激的 CD8+T 细胞表现出以高 IL-10 产生为特征的单功能反应。然而,在恢复期,我们观察到以 CD107a 和 granzyme B 或穿孔素共表达为特征的双功能反应。

结论

尽管促炎反应是 SARS-CoV-2 感染的标志,但 NK 细胞和 CD8+T 细胞的其他表型和功能改变可能与 COVID-19 的结局相关。然而,需要进一步的研究来了解这些改变并指导未来的免疫治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/733b/8604040/c774b8bf4bae/2590-7379-bio-41-s2-5976-gf1.jpg

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