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Severe COVID-19 patients have impaired plasmacytoid dendritic cell-mediated control of SARS-CoV-2-infected cells
medRxiv - Infectious Diseases Pub Date : 2021-10-10 , DOI: 10.1101/2021.09.01.21262969
Manon Venet , Margarida Sa Ribeiro , Elodie Décembre , Alicia Bellomo , Garima Joshi , Marine Villard , David Cluet , Magali Perret , Rémi Pescamona , Helena Paidassi , Thierry Walzer , Omran Allatif , Alexandre Belot , Sophie Assant , Emiliano Ricci , Marlène Dreux

Type I and III interferons (IFN-I/λ) are key antiviral mediators against SARS-CoV-2 infection. Here, we demonstrate that plasmacytoid dendritic cells (pDCs) are the predominant IFN-I/λ source following their sensing of SARS-CoV-2-infected cells. Mechanistically, this short-range sensing by pDCs requires sustained integrin-mediated cell adhesion with infected cells. In turn, pDCs restrict viral spread by an IFN-I/λ response directed toward SARS-CoV-2-infected cells. This specialized function enables pDCs to efficiently turn-off viral replication, likely via a local response at the contact site with infected cells. By exploring the pDC response in SARS-CoV-2 patients, we further demonstrate that pDC responsiveness inversely correlates with the severity of the disease. The pDC response is particularly impaired in severe COVID-19 patients. Overall, we propose that pDC activation is essential to control SARS-CoV-2-infection. Failure to unfold this response could be key to understand severe cases of COVID-19.

中文翻译:

严重的 COVID-19 患者的浆细胞样树突状细胞介导的对 SARS-CoV-2 感染细胞的控制受损

I 型和 III 型干扰素 (IFN-I/λ) 是对抗 SARS-CoV-2 感染的关键抗病毒介质。在这里,我们证明了浆细胞样树突状细胞 (pDC) 是在感知 SARS-CoV-2 感染细胞后的主要 IFN-I/λ 来源。从机制上讲,pDC 的这种短程感应需要持续的整合素介导的细胞与受感染细胞的粘附。反过来,pDC 通过针对 SARS-CoV-2 感染细胞的 IFN-I/λ 反应限制病毒传播。这种特殊的功能使 pDC 能够有效地关闭病毒复制,可能通过与受感染细胞接触部位的局部反应。通过探索 SARS-CoV-2 患者的 pDC 反应,我们进一步证明 pDC 反应性与疾病的严重程度成反比。pDC 反应在严重的 COVID-19 患者中尤其受损。总体而言,我们建议 pDC 激活对于控制 SARS-CoV-2 感染至关重要。未能展开这种反应可能是了解 COVID-19 严重病例的关键。
更新日期:2021-10-12
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