Postgraduate Program in Natural and Synthetic Bioactive Products, Immunology Laboratory of Infectious Diseases, Federal University of Paraiba, João Pessoa, Paraíba 58051-900, Brazil.
Postgraduate Program in Physiology Science, Immunology Laboratory of Infectious Diseases, Department of Cellular and Molecular Biology, Federal University of Paraiba, João Pessoa, Paraíba 58051-900, Brazil.
Cytokine. 2022 Sep;157:155971. doi: 10.1016/j.cyto.2022.155971. Epub 2022 Jul 22.
Natural Killer cells (NK) are crucial in host defense against viruses. There are many unanswered questions about the immune system in COVID-19, especially the mechanisms that contribute to the development of mild or severe forms of the disease. Although NK cells may have an essential role in the pathogenesis of COVID-19, the mechanisms involved in this process are not yet fully elucidated. Here, we demonstrate that CD3CD56 NK cells frequency in the volunteers who recovered from mild COVID-19 (Mild CoV) presented a significant increase compared to the healthy control (HC) and individuals recovering from severe COVID-19 (Severe CoV) groups. Furthermore, distinct IFN profiles in recovered COVID-19 patients with mild or severe clinical forms of the disease were observed in the total NK cells (CD3CD56). In the first group, NK cells express increased levels of IFN-α compared to the severe CoV, while higher production of IFN-γ in severe CoV was found. Moreover, NK cells in mild CoV express more cytolytic granules depicted by granzyme B and perforin. Compared to HC, PBMCs from mild CoV presented higher Ki-67 and TIM-3 production after Pool CoV-2 and Pool Spike CoV-2 peptides stimulus. In addition, non-stimulated PBMCs in the mild CoV group had higher NK TIM-3+ frequency than severe CoV. In the mild CoV group, Pool Spike CoV-2 and Pool CoV-2 peptides stimuli elicited higher granzyme B and perforin coexpression and IFN-α production by PBMCs. However, in severe CoV, Pool Spike CoV-2 reduced the coexpression of granzyme B, perforin, and CD107a suggesting a decrease in the cytotoxic activity of NK cells. Therefore, our study shows that NK cells may have a crucial role in COVID-19 with the involvement of IFN-α and cytotoxic properties that aid in developing qualified immune responses. Furthermore, the data suggest that higher amounts of IFN-γ may be linked to the severity of this disease.
自然杀伤细胞（NK）在宿主防御病毒中起着至关重要的作用。关于 COVID-19 中的免疫系统，仍有许多尚未解答的问题，特别是导致疾病呈现轻度或重度形式的机制。尽管 NK 细胞在 COVID-19 的发病机制中可能具有重要作用，但这一过程涉及的机制尚未完全阐明。在这里，我们证明从轻度 COVID-19（轻度 CoV）中康复的志愿者的 CD3CD56NK 细胞频率与健康对照（HC）和从重度 COVID-19（重度 CoV）中康复的个体相比显著增加。此外，在 NK 细胞中观察到具有轻度或重度临床形式的 COVID-19 患者的不同 IFN 谱。在第一组中，与重度 CoV 相比，NK 细胞表达更高水平的 IFN-α，而在重度 CoV 中发现更高水平的 IFN-γ 产生。此外，轻度 CoV 中的 NK 细胞表达更多的颗粒酶 B 和穿孔素描绘的细胞毒性颗粒。与 HC 相比，来自轻度 CoV 的 PBMC 在 Pool CoV-2 和 Pool Spike CoV-2 肽刺激后表现出更高的 Ki-67 和 TIM-3 产生。此外，与重度 CoV 相比，轻度 CoV 组中非刺激的 PBMC 具有更高的 NK TIM-3+频率。在轻度 CoV 组中，Pool Spike CoV-2 和 Pool CoV-2 肽刺激可引发更高的颗粒酶 B 和穿孔素共表达以及 PBMC 中 IFN-α 的产生。然而，在重度 CoV 中，Pool Spike CoV-2 降低了颗粒酶 B、穿孔素和 CD107a 的共表达，表明 NK 细胞的细胞毒性活性降低。因此，我们的研究表明，NK 细胞可能在 COVID-19 中具有重要作用，涉及 IFN-α 和细胞毒性特性，有助于产生合格的免疫反应。此外，数据表明，较高水平的 IFN-γ 可能与该疾病的严重程度有关。
