TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liver
Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus does not only lead to pulmonary infection but can also infect other organs such as the gut, the kidney, or the liver. Recent studies confirmed that severe cases of COVID-19 a...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1151937/full |
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| author | Jöran Lücke Jöran Lücke Jöran Lücke Mikolaj Nawrocki Mikolaj Nawrocki Mikolaj Nawrocki Josa Schnell Josa Schnell Nicholas Meins Nicholas Meins Fabian Heinrich Fabian Heinrich Tao Zhang Tao Zhang Franziska Bertram Franziska Bertram Franziska Bertram Morsal Sabihi Morsal Sabihi Marius Böttcher Marius Böttcher Marius Böttcher Tom Blankenburg Tom Blankenburg Marie Pfaff Sara Notz Jan Kempski Jan Kempski Jan Kempski Jan Kempski Matthias Reeh Stefan Wolter Oliver Mann Jakob R. Izbicki Marc Lütgehetmann Anna Duprée Anastasios D. Giannou Anastasios D. Giannou Anastasios D. Giannou Benjamin Ondruschka Samuel Huber Samuel Huber Samuel Huber |
| author_facet | Jöran Lücke Jöran Lücke Jöran Lücke Mikolaj Nawrocki Mikolaj Nawrocki Mikolaj Nawrocki Josa Schnell Josa Schnell Nicholas Meins Nicholas Meins Fabian Heinrich Fabian Heinrich Tao Zhang Tao Zhang Franziska Bertram Franziska Bertram Franziska Bertram Morsal Sabihi Morsal Sabihi Marius Böttcher Marius Böttcher Marius Böttcher Tom Blankenburg Tom Blankenburg Marie Pfaff Sara Notz Jan Kempski Jan Kempski Jan Kempski Jan Kempski Matthias Reeh Stefan Wolter Oliver Mann Jakob R. Izbicki Marc Lütgehetmann Anna Duprée Anastasios D. Giannou Anastasios D. Giannou Anastasios D. Giannou Benjamin Ondruschka Samuel Huber Samuel Huber Samuel Huber |
| author_sort | Jöran Lücke |
| collection | DOAJ |
| description | Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus does not only lead to pulmonary infection but can also infect other organs such as the gut, the kidney, or the liver. Recent studies confirmed that severe cases of COVID-19 are often associated with liver damage and liver failure, as well as the systemic upregulation of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα). However, the impact these immune mediators in the liver have on patient survival during SARS-CoV-2 infection is currently unknown. Here, by performing a post-mortem analysis of 45 patients that died from a SARS-CoV-2 infection, we find that an increased expression of TNFA in the liver is associated with elevated mortality. Using publicly available single-cell sequencing datasets, we determined that Kupffer cells and monocytes are the main sources of this TNFα production. Further analysis revealed that TNFα signaling led to the upregulation of pro-inflammatory genes that are associated with an unfavorable outcome. Moreover, high levels of TNFA in the liver were associated with lower levels of interferon alpha and interferon beta. Thus, TNFα signaling in the infected SARS-CoV-2 liver correlates with reduced interferon levels and overall survival time. |
| first_indexed | 2024-04-09T20:20:33Z |
| format | Article |
| id | doaj.art-189b81ba144b45d58c6bedc5167cda2a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T20:20:33Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-189b81ba144b45d58c6bedc5167cda2a2023-03-31T05:45:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-03-011410.3389/fimmu.2023.11519371151937TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liverJöran Lücke0Jöran Lücke1Jöran Lücke2Mikolaj Nawrocki3Mikolaj Nawrocki4Mikolaj Nawrocki5Josa Schnell6Josa Schnell7Nicholas Meins8Nicholas Meins9Fabian Heinrich10Fabian Heinrich11Tao Zhang12Tao Zhang13Franziska Bertram14Franziska Bertram15Franziska Bertram16Morsal Sabihi17Morsal Sabihi18Marius Böttcher19Marius Böttcher20Marius Böttcher21Tom Blankenburg22Tom Blankenburg23Marie Pfaff24Sara Notz25Jan Kempski26Jan Kempski27Jan Kempski28Jan Kempski29Matthias Reeh30Stefan Wolter31Oliver Mann32Jakob R. Izbicki33Marc Lütgehetmann34Anna Duprée35Anastasios D. Giannou36Anastasios D. Giannou37Anastasios D. Giannou38Benjamin Ondruschka39Samuel Huber40Samuel Huber41Samuel Huber42Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyI. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Medical Microbiology, Virology, and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Medical Microbiology, Virology, and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyI. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyI. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyThe Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Medical Microbiology, Virology, and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyI. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyCoronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus does not only lead to pulmonary infection but can also infect other organs such as the gut, the kidney, or the liver. Recent studies confirmed that severe cases of COVID-19 are often associated with liver damage and liver failure, as well as the systemic upregulation of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα). However, the impact these immune mediators in the liver have on patient survival during SARS-CoV-2 infection is currently unknown. Here, by performing a post-mortem analysis of 45 patients that died from a SARS-CoV-2 infection, we find that an increased expression of TNFA in the liver is associated with elevated mortality. Using publicly available single-cell sequencing datasets, we determined that Kupffer cells and monocytes are the main sources of this TNFα production. Further analysis revealed that TNFα signaling led to the upregulation of pro-inflammatory genes that are associated with an unfavorable outcome. Moreover, high levels of TNFA in the liver were associated with lower levels of interferon alpha and interferon beta. Thus, TNFα signaling in the infected SARS-CoV-2 liver correlates with reduced interferon levels and overall survival time.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1151937/fullSARS-CoV-2liverTNFapost-mortemCxcl3Cxcl8 |
| spellingShingle | Jöran Lücke Jöran Lücke Jöran Lücke Mikolaj Nawrocki Mikolaj Nawrocki Mikolaj Nawrocki Josa Schnell Josa Schnell Nicholas Meins Nicholas Meins Fabian Heinrich Fabian Heinrich Tao Zhang Tao Zhang Franziska Bertram Franziska Bertram Franziska Bertram Morsal Sabihi Morsal Sabihi Marius Böttcher Marius Böttcher Marius Böttcher Tom Blankenburg Tom Blankenburg Marie Pfaff Sara Notz Jan Kempski Jan Kempski Jan Kempski Jan Kempski Matthias Reeh Stefan Wolter Oliver Mann Jakob R. Izbicki Marc Lütgehetmann Anna Duprée Anastasios D. Giannou Anastasios D. Giannou Anastasios D. Giannou Benjamin Ondruschka Samuel Huber Samuel Huber Samuel Huber TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liver Frontiers in Immunology SARS-CoV-2 liver TNFa post-mortem Cxcl3 Cxcl8 |
| title | TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liver |
| title_full | TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liver |
| title_fullStr | TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liver |
| title_full_unstemmed | TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liver |
| title_short | TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liver |
| title_sort | tnfα aggravates detrimental effects of sars cov 2 infection in the liver |
| topic | SARS-CoV-2 liver TNFa post-mortem Cxcl3 Cxcl8 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1151937/full |
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