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

Poletti, M.; Treveil, A.; Gul, L.; Modos, D.; Madgwick, M.; Olbei, M.; Bohar, B.; Valdeolivas, A.; Turei, D.; Verstockt, B.; Triana, S.; Alexandrov, T.; Saez-Rodriguez, J.; Stanifer, M. L.; Boulant, S.; Korcsmaros, T.

doi:10.1101/2021.08.09.455656

bioRxiv · 10.1101/2021.08.09.455656

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

Poletti, M.·Treveil, A.·Gul, L.·Modos, D.·Madgwick, M.·Olbei, M.·Bohar, B.·Valdeolivas, A.·Turei, D.·Verstockt, B.·Triana, S.·Alexandrov, T.·Saez-Rodriguez, J.·Stanifer, M. L.·Boulant, S.·Korcsmaros, T.

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Abstract

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.

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Poletti, M., Treveil, A., Gul, L., Modos, D., Madgwick, M., Olbei, M., Bohar, B., Valdeolivas, A., Turei, D., Verstockt, B., Triana, S., Alexandrov, T., Saez-Rodriguez, J., Stanifer, M. L., Boulant, S., Korcsmaros, T.. 2021-08-09. Reprogramming of the intestinal epithelial-immune cell interactome during SARS-CoV-2 infection. https://doi.org/10.1101/2021.08.09.455656

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