急性严重急性呼吸综合征冠状病毒 2 感染损害树突状细胞和 T 细胞应答。

Acute SARS-CoV-2 Infection Impairs Dendritic Cell and T Cell Responses.

机构信息

AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), People's Republic of China; Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China.

Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China.

出版信息

Immunity. 2020 Oct 13;53(4):864-877.e5. doi: 10.1016/j.immuni.2020.07.026. Epub 2020 Aug 4.

Abstract

The SARS-CoV-2 pandemic has resulted in millions of infections, yet the role of host immune responses in early COVID-19 pathogenesis remains unclear. By investigating 17 acute and 24 convalescent patients, we found that acute SARS-CoV-2 infection resulted in broad immune cell reduction including T, natural killer, monocyte, and dendritic cells (DCs). DCs were significantly reduced with functional impairment, and ratios of conventional DCs to plasmacytoid DCs were increased among acute severe patients. Besides lymphocytopenia, although neutralizing antibodies were rapidly and abundantly generated in patients, there were delayed receptor binding domain (RBD)- and nucleocapsid protein (NP)-specific T cell responses during the first 3 weeks after symptoms onset. Moreover, acute RBD- and NP-specific T cell responses included relatively more CD4 T cells than CD8 T cells. Our findings provided evidence that impaired DCs, together with timely inverted strong antibody but weak CD8 T cell responses, could contribute to acute COVID-19 pathogenesis and have implications for vaccine development.

摘要

SARS-CoV-2 大流行导致了数百万人感染,但宿主免疫反应在 COVID-19 发病机制中的早期作用仍不清楚。通过对 17 名急性和 24 名恢复期患者的研究,我们发现急性 SARS-CoV-2 感染导致广泛的免疫细胞减少,包括 T 细胞、自然杀伤细胞、单核细胞和树突状细胞(DC)。DC 显著减少,功能受损,急性重症患者的常规 DC 与浆细胞样 DC 的比例增加。除了淋巴细胞减少症,尽管中和抗体在患者体内迅速且大量产生,但在症状出现后的前 3 周内,受体结合域(RBD)和核衣壳蛋白(NP)特异性 T 细胞反应延迟。此外,急性 RBD 和 NP 特异性 T 细胞反应包括相对较多的 CD4 T 细胞,而不是 CD8 T 细胞。我们的研究结果提供了证据,表明受损的 DC 与及时产生的强烈抗体但较弱的 CD8 T 细胞反应一起,可能导致急性 COVID-19 的发病机制,并对疫苗的开发具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f65c/7402670/b9d760cb5714/fx1_lrg.jpg

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