Mapping the epithelial–immune cell interactome upon infection in the gut and the upper airways
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....
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-05-01
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| Series: | npj Systems Biology and Applications |
| Online Access: | https://doi.org/10.1038/s41540-022-00224-x |
| _version_ | 1818191309554319360 |
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| author | Martina Poletti Agatha Treveil Luca Csabai Leila Gul Dezso Modos Matthew Madgwick Marton Olbei Balazs Bohar Alberto Valdeolivas Denes Turei Bram Verstockt Sergio Triana Theodore Alexandrov Julio Saez-Rodriguez Megan L. Stanifer Steeve Boulant Tamas Korcsmaros |
| author_facet | Martina Poletti Agatha Treveil Luca Csabai Leila Gul Dezso Modos Matthew Madgwick Marton Olbei Balazs Bohar Alberto Valdeolivas Denes Turei Bram Verstockt Sergio Triana Theodore Alexandrov Julio Saez-Rodriguez Megan L. Stanifer Steeve Boulant Tamas Korcsmaros |
| author_sort | Martina Poletti |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T00:12:34Z |
| format | Article |
| id | doaj.art-738ae418fdc748b4b520a8a08ccc3aac |
| institution | Directory Open Access Journal |
| issn | 2056-7189 |
| language | English |
| last_indexed | 2024-12-12T00:12:34Z |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Systems Biology and Applications |
| spelling | doaj.art-738ae418fdc748b4b520a8a08ccc3aac2022-12-22T00:44:56ZengNature Portfolionpj Systems Biology and Applications2056-71892022-05-018111910.1038/s41540-022-00224-xMapping the epithelial–immune cell interactome upon infection in the gut and the upper airwaysMartina Poletti0Agatha Treveil1Luca Csabai2Leila Gul3Dezso Modos4Matthew Madgwick5Marton Olbei6Balazs Bohar7Alberto Valdeolivas8Denes Turei9Bram Verstockt10Sergio Triana11Theodore Alexandrov12Julio Saez-Rodriguez13Megan L. Stanifer14Steeve Boulant15Tamas Korcsmaros16Earlham Institute, Norwich Research ParkEarlham Institute, Norwich Research ParkEarlham Institute, Norwich Research ParkEarlham Institute, Norwich Research ParkEarlham Institute, Norwich Research ParkEarlham Institute, Norwich Research ParkEarlham Institute, Norwich Research ParkEarlham Institute, Norwich Research ParkFaculty of Medicine, Heidelberg UniversityFaculty of Medicine, Heidelberg UniversityDepartment of Gastroenterology and Hepatology, University Hospitals Leuven, KU LeuvenStructural and Computational Biology Unit, European Molecular Biology LaboratorySkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San DiegoFaculty of Medicine, Heidelberg UniversityDepartment of Infectious Diseases, Heidelberg University Hospital HeidelbergDepartment of Infectious Diseases, Heidelberg University Hospital HeidelbergEarlham Institute, Norwich Research ParkAbstract 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.https://doi.org/10.1038/s41540-022-00224-x |
| spellingShingle | Martina Poletti Agatha Treveil Luca Csabai Leila Gul Dezso Modos Matthew Madgwick Marton Olbei Balazs Bohar Alberto Valdeolivas Denes Turei Bram Verstockt Sergio Triana Theodore Alexandrov Julio Saez-Rodriguez Megan L. Stanifer Steeve Boulant Tamas Korcsmaros Mapping the epithelial–immune cell interactome upon infection in the gut and the upper airways npj Systems Biology and Applications |
| title | Mapping the epithelial–immune cell interactome upon infection in the gut and the upper airways |
| title_full | Mapping the epithelial–immune cell interactome upon infection in the gut and the upper airways |
| title_fullStr | Mapping the epithelial–immune cell interactome upon infection in the gut and the upper airways |
| title_full_unstemmed | Mapping the epithelial–immune cell interactome upon infection in the gut and the upper airways |
| title_short | Mapping the epithelial–immune cell interactome upon infection in the gut and the upper airways |
| title_sort | mapping the epithelial immune cell interactome upon infection in the gut and the upper airways |
| url | https://doi.org/10.1038/s41540-022-00224-x |
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