Reprogramming of the intestinal epithelial-immune cell interactome during SARS-CoV-2 infection
Reprogramming of the intestinal epithelial-immune cell interactome during SARS-CoV-2 infection
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DOI：
10.1101/2021.08.09.455656
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发表时间：
2021-08
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通讯作者：
M. Poletti;A. Treveil;L. Csabai;L. Gul;D. Módos;M. Madgwick;M. Olbei;B. Bohár;Alberto Valdeolivas;D. Turei;B. Verstockt;Sergio Triana;T. Alexandrov;J. Saez-Rodriguez;M. Stanifer;S. Boulant;T. Korcsmáros
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作者：
M. Poletti;A. Treveil;L. Csabai;L. Gul;D. Módos;M. Madgwick;M. Olbei;B. Bohár;Alberto Valdeolivas;D. Turei;B. Verstockt;Sergio Triana;T. Alexandrov;J. Saez-Rodriguez;M. Stanifer;S. Boulant;T. Korcsmáros
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是一个前所未有的全球性健康问题。虽然感染的主要部位是肺部，但越来越多的证据表明肠上皮细胞起着至关重要的作用。然而，病毒感染的确切影响和肠上皮-免疫细胞相互作用在介导炎症反应中的作用尚不清楚。在这项工作中，我们将网络生物学方法应用于来自SARS-CoV-2感染的人类回肠和结肠类器官的单细胞RNA-seq数据，以研究肠上皮细胞感染后改变的细胞内途径如何导致修饰的上皮免疫串扰。我们指出，特定的上皮免疫相互作用，可以帮助SARS-CoV-2逃避免疫反应。通过将我们的数据与现有的实验数据相结合，我们提供了一组可能在感染后驱动炎症反应的上皮配体。我们对细胞内和细胞间分子网络的综合分析有助于发现潜在的药物靶点，并建议将肠道中现有的抗炎疗法作为对抗COVID-19的有前景的药物再利用策略。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents an unprecedented worldwide health problem. Although the primary site of infection is the lung, growing evidence points towards a crucial role of the intestinal epithelium. Yet, the exact effects of viral infection and the role of intestinal epithelial-immune cell interactions in mediating the inflammatory response are not known. In this work, we apply network biology approaches to single-cell RNA-seq data from SARS-CoV-2 infected human ileal and colonic organoids to investigate how altered intracellular pathways upon infection in intestinal enterocytes leads to modified epithelial-immune crosstalk. We point out specific epithelial-immune interactions which could help SARS-CoV-2 evade the immune response. By integrating our data with existing experimental data, we provide a set of epithelial ligands likely to drive the inflammatory response upon infection. Our integrated analysis of intra- and inter-cellular molecular networks contribute to finding potential drug targets, and suggest using existing anti-inflammatory therapies in the gut as promising drug repurposing strategies against COVID-19.