Marzena Lenart, Magdalena Rutkowska-Zapała, Maciej Siedlar
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引用次数: 0
摘要
自然杀伤(NK)细胞在控制病毒感染方面发挥着至关重要的作用。能否在不事先免疫的情况下杀死受感染的细胞,同时又对自身的健康细胞具有耐受性,这取决于种系编码的表面受体的平衡。NK 细胞受体分为激活型和抑制型,激活型受体可导致 NK 细胞活化并产生细胞毒性和促炎活性,抑制型受体则可提供对靶细胞的耐受性。抑制性受体发出的信号占主导地位,NK 细胞的激活需要激活性受体的刺激。在病毒感染中,NK 细胞与受感染细胞的相互作用可导致激活、记忆型 NK 细胞分化或 NK 细胞衰竭,这构成了病毒免疫逃避机制之一。所有这些状态都与 NK 细胞受体表达的调节有关。在这篇综述中,我们总结了目前关于 NK 细胞受体及其在病毒感染控制中作用的知识,以及在急性或慢性感染中观察到的受体表达变化。我们介绍了最近发现的 SARS-CoV-2 介导的 NK 细胞受体表达调节,并将其与其他人类病毒感染进行了比较。最后,由于对 NK 细胞受体活化的调节有望为目前使用的抗病毒疗法提供新的补充,我们简要讨论了分别应用活化受体和抑制受体的激动剂或拮抗剂的临床意义和未来前景。总之,我们的综述表明,尽管人们对 NK 细胞受体生物学知之甚少,但仍需要更深入地了解 NK 细胞受体在病毒感染中的作用。
Natural killer (NK) cells play a crucial role in controlling viral infections. The ability to kill infected cells without prior immunization, yet being tolerant to self, healthy cells, depends on the balance of germ-line encoded surface receptors. NK-cell receptors are divided into either activating, leading to activation of NK cell and its cytotoxic and pro-inflammatory activity, or inhibitory, providing tolerance for a target cell. The signals from inhibitory receptors dominate and NK-cell activation requires stimulation of activating receptors. In viral infections, NK-cell interaction with infected cells can result in activation, memory-like NK-cell differentiation, or NK-cell exhaustion, which constitutes one of the viral immune evasion mechanisms. All of these states are associated with the modulation of NK-cell receptor expression. In this review, we summarize the current knowledge of NK-cell receptors and their role in viral infection control, as well as the alterations of their expression observed in acute or chronic infections. We present recently discovered SARS-CoV-2-mediated modulation of NK-cell receptor expression and compare them with other human viral infections. Finally, since modulation of NK-cell receptor activation gives a promising addition to currently used antiviral therapies, we briefly discuss the clinical significance and future perspective of the application of agonists or antagonists of activating and inhibitory receptors, respectively. In sum, our review shows that although much is known about NK-cell receptor biology, a deeper understanding of NK-cell receptors role in viral infections is still needed.
期刊介绍:
Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice.
The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.