Department of Molecular & Biomedical Sciences University of Maine, Orono, ME, USA; Tufts University School of Medicine, Boston, MA, USA; IT Bio, LLC, Nest.Bio Labs, Cambridge, MA, USA.
Mol Immunol. 2021 Jul;135:268-275. doi: 10.1016/j.molimm.2021.04.021. Epub 2021 Apr 30.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have triggered global pandemic that continue to impact adversely human health. New understanding has emerged about the innate and adaptive immune responses elicited in SARS-CoV-2 infection. The understanding of innate immune responses generated in hosts early in SARS-CoV-2 infection is vital for treatment efforts. Antiviral cytokines are released by innate immune cells in response to viral infections that play a pivotal role in limiting viral replication, pathology and generating optimal adaptive immune responses alongside the long-term memory responses against reinfections. One aspect of innate immune response generated against SARS-CoV-2 in vivo and which has received much attention has been high proinflammatory cytokine release in COVID-19 patients. Another vital discovery has been that the antiviral cytokine type I Interferon (IFN) family IFN-α mediates upregulation of angiotensin converting enzyme 2 (ACE2) membrane protein in airway epithelial cells. ACE2 is a receptor that SARS-CoV-2 binds to infect host cells. New understanding has emerged about the mechanism of SARS-CoV-2 induced exaggerated proinflammatory cytokine release as well as transcriptional regulation of ACE2. This review discusses various mechanisms underlying SARS-CoV-2 induced exaggerated proinflammatory cytokine response as well as transcriptional regulation of ACE2 receptor. We further elaborate on adaptive and memory responses generated against SARS-CoV-2.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染引发了全球大流行，持续对人类健康产生不利影响。人们对 SARS-CoV-2 感染引起的固有和适应性免疫反应有了新的认识。了解宿主在 SARS-CoV-2 感染早期产生的固有免疫反应对于治疗工作至关重要。抗病毒细胞因子是固有免疫细胞对病毒感染的反应释放的，在限制病毒复制、病理学和产生最佳适应性免疫反应以及针对再感染的长期记忆反应方面发挥着关键作用。固有免疫反应的一个方面是针对 SARS-CoV-2 在体内产生的，并且受到了广泛关注，即 COVID-19 患者中促炎细胞因子的大量释放。另一个重要发现是，抗病毒细胞因子 I 型干扰素（IFN）家族 IFN-α介导气道上皮细胞中血管紧张素转换酶 2（ACE2）膜蛋白的上调。ACE2 是 SARS-CoV-2 结合感染宿主细胞的受体。人们对 SARS-CoV-2 诱导的促炎细胞因子过度释放的机制以及 ACE2 受体的转录调控有了新的认识。本综述讨论了 SARS-CoV-2 诱导的促炎细胞因子反应过度以及 ACE2 受体转录调控的各种机制。我们进一步阐述了针对 SARS-CoV-2 产生的适应性和记忆反应。
