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Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and T cell priming
RATIONALE: Sepsis, a global health burden, is often complicated by viral infections leading to increased long-term morbidity and mortality. Interleukin-3 (IL-3) has been identified as an important mediator amplifying acute inflammation in sepsis; however, its function in the host response to viral i...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9996195/ https://www.ncbi.nlm.nih.gov/pubmed/36911737 http://dx.doi.org/10.3389/fimmu.2023.1140630 |
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author | Bénard, Alan Hansen, Frederik J. Uhle, Florian Klösch, Bettina Czubayko, Franziska Mittelstädt, Anke Jacobsen, Anne David, Paul Podolska, Malgorzata J. Anthuber, Anna Swierzy, Izabela Schaack, Dominik Mühl-Zürbes, Petra Steinkasserer, Alexander Weyand, Michael Weigand, Markus A. Brenner, Thorsten Krautz, Christian Grützmann, Robert Weber, Georg F. |
author_facet | Bénard, Alan Hansen, Frederik J. Uhle, Florian Klösch, Bettina Czubayko, Franziska Mittelstädt, Anke Jacobsen, Anne David, Paul Podolska, Malgorzata J. Anthuber, Anna Swierzy, Izabela Schaack, Dominik Mühl-Zürbes, Petra Steinkasserer, Alexander Weyand, Michael Weigand, Markus A. Brenner, Thorsten Krautz, Christian Grützmann, Robert Weber, Georg F. |
author_sort | Bénard, Alan |
collection | PubMed |
description | RATIONALE: Sepsis, a global health burden, is often complicated by viral infections leading to increased long-term morbidity and mortality. Interleukin-3 (IL-3) has been identified as an important mediator amplifying acute inflammation in sepsis; however, its function in the host response to viral infections during sepsis remains elusive. OBJECTIVES: To investigate the role of IL-3 during viral pneumonia in sepsis. METHODS: We included septic patients from two different cohorts and used in vitro and in vivo assays. The obtained data were substantiated using a second model (SARS-CoV-2 infections). MEASUREMENTS AND MAIN RESULTS: Low plasma IL-3 levels were associated with increased herpes simplex virus (HSV) airway infections in septic patients, resulting in reduced overall survival. Likewise, Il-3-deficient septic mice were more susceptible to pulmonary HSV-1 infection and exhibited higher pulmonary inflammation than control mice. Mechanistically, IL-3 increases innate antiviral immunity by promoting the recruitment of circulating plasmacytoid dendritic cells (pDCs) into the airways and by enhancing pDC-mediated T cell activation upon viral stimulation. Interestingly, the ability of IL-3 to improve adaptive immunity was confirmed in patients with SARS-CoV-2 infections. CONCLUSION: Our study identifies IL-3 as a predictive disease marker for viral reactivation in sepsis and reveals that IL-3 improves antiviral immunity by enhancing the recruitment and the function of pDCs. |
format | Online Article Text |
id | pubmed-9996195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99961952023-03-10 Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and T cell priming Bénard, Alan Hansen, Frederik J. Uhle, Florian Klösch, Bettina Czubayko, Franziska Mittelstädt, Anke Jacobsen, Anne David, Paul Podolska, Malgorzata J. Anthuber, Anna Swierzy, Izabela Schaack, Dominik Mühl-Zürbes, Petra Steinkasserer, Alexander Weyand, Michael Weigand, Markus A. Brenner, Thorsten Krautz, Christian Grützmann, Robert Weber, Georg F. Front Immunol Immunology RATIONALE: Sepsis, a global health burden, is often complicated by viral infections leading to increased long-term morbidity and mortality. Interleukin-3 (IL-3) has been identified as an important mediator amplifying acute inflammation in sepsis; however, its function in the host response to viral infections during sepsis remains elusive. OBJECTIVES: To investigate the role of IL-3 during viral pneumonia in sepsis. METHODS: We included septic patients from two different cohorts and used in vitro and in vivo assays. The obtained data were substantiated using a second model (SARS-CoV-2 infections). MEASUREMENTS AND MAIN RESULTS: Low plasma IL-3 levels were associated with increased herpes simplex virus (HSV) airway infections in septic patients, resulting in reduced overall survival. Likewise, Il-3-deficient septic mice were more susceptible to pulmonary HSV-1 infection and exhibited higher pulmonary inflammation than control mice. Mechanistically, IL-3 increases innate antiviral immunity by promoting the recruitment of circulating plasmacytoid dendritic cells (pDCs) into the airways and by enhancing pDC-mediated T cell activation upon viral stimulation. Interestingly, the ability of IL-3 to improve adaptive immunity was confirmed in patients with SARS-CoV-2 infections. CONCLUSION: Our study identifies IL-3 as a predictive disease marker for viral reactivation in sepsis and reveals that IL-3 improves antiviral immunity by enhancing the recruitment and the function of pDCs. Frontiers Media S.A. 2023-02-22 /pmc/articles/PMC9996195/ /pubmed/36911737 http://dx.doi.org/10.3389/fimmu.2023.1140630 Text en Copyright © 2023 Bénard, Hansen, Uhle, Klösch, Czubayko, Mittelstädt, Jacobsen, David, Podolska, Anthuber, Swierzy, Schaack, Mühl-Zürbes, Steinkasserer, Weyand, Weigand, Brenner, Krautz, Grützmann and Weber https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Bénard, Alan Hansen, Frederik J. Uhle, Florian Klösch, Bettina Czubayko, Franziska Mittelstädt, Anke Jacobsen, Anne David, Paul Podolska, Malgorzata J. Anthuber, Anna Swierzy, Izabela Schaack, Dominik Mühl-Zürbes, Petra Steinkasserer, Alexander Weyand, Michael Weigand, Markus A. Brenner, Thorsten Krautz, Christian Grützmann, Robert Weber, Georg F. Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and T cell priming |
title | Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and T cell priming |
title_full | Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and T cell priming |
title_fullStr | Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and T cell priming |
title_full_unstemmed | Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and T cell priming |
title_short | Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and T cell priming |
title_sort | interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and t cell priming |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9996195/ https://www.ncbi.nlm.nih.gov/pubmed/36911737 http://dx.doi.org/10.3389/fimmu.2023.1140630 |
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