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Mapping the epithelial-immune cell interactome upon infection in the gut and the upper airways.
NPJ Syst Biol Appl. 2022 05 02; 8(1):15.NS

Abstract

Increasing evidence points towards the key role of the epithelium in the systemic and over-activated immune response to viral infection, including SARS-CoV-2 infection. Yet, how viral infection alters epithelial-immune cell interactions regulating inflammatory responses, is not well known. Available experimental approaches are insufficient to properly analyse this complex system, and computational predictions and targeted data integration are needed as an alternative approach. In this work, we propose an integrated computational biology framework that models how infection alters intracellular signalling of epithelial cells and how this change impacts the systemic immune response through modified interactions between epithelial cells and local immune cell populations. As a proof-of-concept, we focused on the role of intestinal and upper-airway epithelial infection. To characterise the modified epithelial-immune interactome, we integrated intra- and intercellular networks with single-cell RNA-seq data from SARS-CoV-2 infected human ileal and colonic organoids as well as from infected airway ciliated epithelial cells. This integrated methodology has proven useful to point out specific epithelial-immune interactions driving inflammation during disease response, and propose relevant molecular targets to guide focused experimental analysis.

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Authors+Show Affiliations

Earlham Institute, Norwich Research Park, Norwich, UK. Quadram Institute Bioscience, Norwich Research Park, Norwich, UK.

Earlham Institute, Norwich Research Park, Norwich, UK. Quadram Institute Bioscience, Norwich Research Park, Norwich, UK.

Earlham Institute, Norwich Research Park, Norwich, UK. Department of Genetics, Eotvos Lorand University, Budapest, Hungary.

Earlham Institute, Norwich Research Park, Norwich, UK.

Earlham Institute, Norwich Research Park, Norwich, UK. Quadram Institute Bioscience, Norwich Research Park, Norwich, UK.

Earlham Institute, Norwich Research Park, Norwich, UK. Quadram Institute Bioscience, Norwich Research Park, Norwich, UK.

Earlham Institute, Norwich Research Park, Norwich, UK. Quadram Institute Bioscience, Norwich Research Park, Norwich, UK.

Earlham Institute, Norwich Research Park, Norwich, UK. Department of Genetics, Eotvos Lorand University, Budapest, Hungary.

Faculty of Medicine, Heidelberg University, Heidelberg, Germany. Institute for Computational Biomedicine, Heidelberg University Hospital, Heidelberg, Germany.

Faculty of Medicine, Heidelberg University, Heidelberg, Germany. Institute for Computational Biomedicine, Heidelberg University Hospital, Heidelberg, Germany.

Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. Department of Chronic Diseases and Metabolism, Translational Research in GI disorders, KU Leuven, Leuven, Belgium.

Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences, Heidelberg, Germany.

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA. Molecular Medicine Partnership Unit (MMPU), European Molecular Biology Laboratory, Heidelberg, Germany.

Saez-Rodriguez J

Faculty of Medicine, Heidelberg University, Heidelberg, Germany. Institute for Computational Biomedicine, Heidelberg University Hospital, Heidelberg, Germany. Molecular Medicine Partnership Unit (MMPU), European Molecular Biology Laboratory, Heidelberg, Germany.

Department of Infectious Diseases, Heidelberg University Hospital Heidelberg, Heidelberg, Germany.

Department of Infectious Diseases, Heidelberg University Hospital Heidelberg, Heidelberg, Germany.

Earlham Institute, Norwich Research Park, Norwich, UK. t.korcsmaros@imperial.ac.uk. Quadram Institute Bioscience, Norwich Research Park, Norwich, UK. t.korcsmaros@imperial.ac.uk. Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. t.korcsmaros@imperial.ac.uk.

MeSH

COVID-19Epithelial CellsHumansSARS-CoV-2Signal TransductionVirus Diseases

Pub Type(s)

Journal Article

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35501398

Citation

Poletti, Martina, et al. "Mapping the Epithelial-immune Cell Interactome Upon Infection in the Gut and the Upper Airways." NPJ Systems Biology and Applications, vol. 8, no. 1, 2022, p. 15.

Poletti M, Treveil A, Csabai L, et al. Mapping the epithelial-immune cell interactome upon infection in the gut and the upper airways. NPJ Syst Biol Appl. 2022;8(1):15.

Poletti, M., Treveil, A., Csabai, L., 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. (2022). Mapping the epithelial-immune cell interactome upon infection in the gut and the upper airways. NPJ Systems Biology and Applications, 8(1), 15. https://doi.org/10.1038/s41540-022-00224-x

Poletti M, et al. Mapping the Epithelial-immune Cell Interactome Upon Infection in the Gut and the Upper Airways. NPJ Syst Biol Appl. 2022 05 2;8(1):15. PubMed PMID: 35501398.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Mapping the epithelial-immune cell interactome upon infection in the gut and the upper airways. AU - Poletti,Martina, AU - Treveil,Agatha, AU - Csabai,Luca, AU - Gul,Leila, AU - Modos,Dezso, AU - Madgwick,Matthew, AU - Olbei,Marton, AU - Bohar,Balazs, AU - Valdeolivas,Alberto, AU - Turei,Denes, AU - Verstockt,Bram, AU - Triana,Sergio, AU - Alexandrov,Theodore, AU - Saez-Rodriguez,Julio, AU - Stanifer,Megan L, AU - Boulant,Steeve, AU - Korcsmaros,Tamas, Y1 - 2022/05/02/ PY - 2021/11/05/received PY - 2022/04/04/accepted PY - 2022/5/2/entrez PY - 2022/5/3/pubmed PY - 2022/5/6/medline SP - 15 EP - 15 JF - NPJ systems biology and applications JO - NPJ Syst Biol Appl VL - 8 IS - 1 N2 - Increasing evidence points towards the key role of the epithelium in the systemic and over-activated immune response to viral infection, including SARS-CoV-2 infection. Yet, how viral infection alters epithelial-immune cell interactions regulating inflammatory responses, is not well known. Available experimental approaches are insufficient to properly analyse this complex system, and computational predictions and targeted data integration are needed as an alternative approach. In this work, we propose an integrated computational biology framework that models how infection alters intracellular signalling of epithelial cells and how this change impacts the systemic immune response through modified interactions between epithelial cells and local immune cell populations. As a proof-of-concept, we focused on the role of intestinal and upper-airway epithelial infection. To characterise the modified epithelial-immune interactome, we integrated intra- and intercellular networks with single-cell RNA-seq data from SARS-CoV-2 infected human ileal and colonic organoids as well as from infected airway ciliated epithelial cells. This integrated methodology has proven useful to point out specific epithelial-immune interactions driving inflammation during disease response, and propose relevant molecular targets to guide focused experimental analysis. SN - 2056-7189 UR - https://www.unboundmedicine.com/medline/citation/35501398/Mapping_the_epithelial_immune_cell_interactome_upon_infection_in_the_gut_and_the_upper_airways_ DB - PRIME DP - Unbound Medicine ER -