Reprogramming of the intestinal epithelial-immune cell interactome during SARS-CoV-2 infection

Poletti, Martina; Treveil, Agatha; Csabai, Luca; Gul, Leila; Modos, Dezso; Madgwick, Matthew; Olbei, Marton; Bohar, Balazs; Valdeolivas, Alberto; Turei, Denes; Verstockt, Bram; Triana, Sergio; Alexandrov, Theodore; Saez-Rodriguez, Julio; Stanifer, Megan L.; Boulant, Steeve; Korcsmaros, Tamas

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.