Laura Chaillot, Marie-Lise Blondot, Patricia Recordon-Pinson, Isabelle Pellegrin, Andrea Boizard-Moracchini, Myroslava Sliusar, Teo Leboucq, Nadege Pujol, Marie-Line Andreola, Fabrice Bonnet, Gaelle Recher, Laetitia Andrique, Pierre Nassoy, Thomas Mathivet, Andreas Bikfalvi
BRIC INSERM U1312, Université de Bordeaux, Pessac, 33615, France.
MFP Laboratory, UMR5234, CNRS Université de Bordeaux, Bordeaux, France.
Sci Rep. 2025 Jul 1;15(1):21129. doi: 10.1038/s41598-025-08329-z.
The blood vessel network is heavily impacted by SARS-CoV-2 infection. How SARS-CoV-2 contributes to vascular inflammation and whether epithelio-endothelial cross-talk is involved remain unclear. We investigated in detail the interaction between SARS-CoV-2 and the vasculature using 2D and 3D vesseloid in vitro models. We first assessed whether SARS-CoV-2 is able to directly infect endothelial cells. In the absence of ACE2 in endothelial cells, no productive infection was detected. Low uptake of viral particles by ACE2-overexpressing endothelial cells was observed without efficient viral production. Thus, the indirect effect of SARS-CoV-2 infection may involve epithelio-endothelial cell cross-talk. After infection of the epithelial cells, a significant inflammatory response was detected in the endothelial cells. CXCL10 was the most highly expressed proinflammatory cytokine involved in this intercellular communication, and its function was subsequently explored. Finally, the clinical relevance of our findings was confirmed in two patient cohorts.
血管网络受到严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的严重影响。SARS-CoV-2如何导致血管炎症以及上皮-内皮细胞间相互作用是否参与其中仍不清楚。我们使用二维和三维类血管体外模型详细研究了SARS-CoV-2与脉管系统之间的相互作用。我们首先评估了SARS-CoV-2是否能够直接感染内皮细胞。在内皮细胞中不存在血管紧张素转换酶2（ACE2）的情况下，未检测到有效感染。在过表达ACE2的内皮细胞中观察到病毒颗粒摄取率低，且没有高效的病毒产生。因此，SARS-CoV-2感染的间接效应可能涉及上皮-内皮细胞间相互作用。上皮细胞感染后，在内皮细胞中检测到显著的炎症反应。CXC趋化因子配体10（CXCL10）是参与这种细胞间通讯的表达最高的促炎细胞因子，随后对其功能进行了探索。最后，我们的研究结果在两个患者队列中得到了临床相关性验证。
