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Bacterial vesicles block viral replication in macrophages via TLR4-TRIF-axis
Gram-negative bacteria naturally secrete nano-sized outer membrane vesicles (OMVs), which are important mediators of communication and pathogenesis. OMV uptake by host cells activates TLR signalling via transported PAMPs. As important resident immune cells, alveolar macrophages are located at the ai...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045439/ https://www.ncbi.nlm.nih.gov/pubmed/36978183 http://dx.doi.org/10.1186/s12964-023-01086-4 |
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author | Bierwagen, Jeff Wiegand, Marie Laakmann, Katrin Danov, Olga Limburg, Hannah Herbel, Stefanie Muriel Heimerl, Thomas Dorna, Jens Jonigk, Danny Preußer, Christian Bertrams, Wilhelm Braun, Armin Sewald, Katherina Schulte, Leon N. Bauer, Stefan Pogge von Strandmann, Elke Böttcher-Friebertshäuser, Eva Schmeck, Bernd Jung, Anna Lena |
author_facet | Bierwagen, Jeff Wiegand, Marie Laakmann, Katrin Danov, Olga Limburg, Hannah Herbel, Stefanie Muriel Heimerl, Thomas Dorna, Jens Jonigk, Danny Preußer, Christian Bertrams, Wilhelm Braun, Armin Sewald, Katherina Schulte, Leon N. Bauer, Stefan Pogge von Strandmann, Elke Böttcher-Friebertshäuser, Eva Schmeck, Bernd Jung, Anna Lena |
author_sort | Bierwagen, Jeff |
collection | PubMed |
description | Gram-negative bacteria naturally secrete nano-sized outer membrane vesicles (OMVs), which are important mediators of communication and pathogenesis. OMV uptake by host cells activates TLR signalling via transported PAMPs. As important resident immune cells, alveolar macrophages are located at the air-tissue interface where they comprise the first line of defence against inhaled microorganisms and particles. To date, little is known about the interplay between alveolar macrophages and OMVs from pathogenic bacteria. The immune response to OMVs and underlying mechanisms are still elusive. Here, we investigated the response of primary human macrophages to bacterial vesicles (Legionella pneumophila, Klebsiella pneumoniae, Escherichia coli, Salmonella enterica, Streptococcus pneumoniae) and observed comparable NF-κB activation across all tested vesicles. In contrast, we describe differential type I IFN signalling with prolonged STAT1 phosphorylation and strong Mx1 induction, blocking influenza A virus replication only for Klebsiella, E.coli and Salmonella OMVs. OMV-induced antiviral effects were less pronounced for endotoxin-free Clear coli OMVs and Polymyxin-treated OMVs. LPS stimulation could not mimic this antiviral status, while TRIF knockout abrogated it. Importantly, supernatant from OMV-treated macrophages induced an antiviral response in alveolar epithelial cells (AEC), suggesting OMV-induced intercellular communication. Finally, results were validated in an ex vivo infection model with primary human lung tissue. In conclusion, Klebsiella, E.coli and Salmonella OMVs induce antiviral immunity in macrophages via TLR4-TRIF-signaling to reduce viral replication in macrophages, AECs and lung tissue. These gram-negative bacteria induce antiviral immunity in the lung through OMVs, with a potential decisive and tremendous impact on bacterial and viral coinfection outcome. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-023-01086-4. |
format | Online Article Text |
id | pubmed-10045439 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-100454392023-03-29 Bacterial vesicles block viral replication in macrophages via TLR4-TRIF-axis Bierwagen, Jeff Wiegand, Marie Laakmann, Katrin Danov, Olga Limburg, Hannah Herbel, Stefanie Muriel Heimerl, Thomas Dorna, Jens Jonigk, Danny Preußer, Christian Bertrams, Wilhelm Braun, Armin Sewald, Katherina Schulte, Leon N. Bauer, Stefan Pogge von Strandmann, Elke Böttcher-Friebertshäuser, Eva Schmeck, Bernd Jung, Anna Lena Cell Commun Signal Research Gram-negative bacteria naturally secrete nano-sized outer membrane vesicles (OMVs), which are important mediators of communication and pathogenesis. OMV uptake by host cells activates TLR signalling via transported PAMPs. As important resident immune cells, alveolar macrophages are located at the air-tissue interface where they comprise the first line of defence against inhaled microorganisms and particles. To date, little is known about the interplay between alveolar macrophages and OMVs from pathogenic bacteria. The immune response to OMVs and underlying mechanisms are still elusive. Here, we investigated the response of primary human macrophages to bacterial vesicles (Legionella pneumophila, Klebsiella pneumoniae, Escherichia coli, Salmonella enterica, Streptococcus pneumoniae) and observed comparable NF-κB activation across all tested vesicles. In contrast, we describe differential type I IFN signalling with prolonged STAT1 phosphorylation and strong Mx1 induction, blocking influenza A virus replication only for Klebsiella, E.coli and Salmonella OMVs. OMV-induced antiviral effects were less pronounced for endotoxin-free Clear coli OMVs and Polymyxin-treated OMVs. LPS stimulation could not mimic this antiviral status, while TRIF knockout abrogated it. Importantly, supernatant from OMV-treated macrophages induced an antiviral response in alveolar epithelial cells (AEC), suggesting OMV-induced intercellular communication. Finally, results were validated in an ex vivo infection model with primary human lung tissue. In conclusion, Klebsiella, E.coli and Salmonella OMVs induce antiviral immunity in macrophages via TLR4-TRIF-signaling to reduce viral replication in macrophages, AECs and lung tissue. These gram-negative bacteria induce antiviral immunity in the lung through OMVs, with a potential decisive and tremendous impact on bacterial and viral coinfection outcome. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-023-01086-4. BioMed Central 2023-03-28 /pmc/articles/PMC10045439/ /pubmed/36978183 http://dx.doi.org/10.1186/s12964-023-01086-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Bierwagen, Jeff Wiegand, Marie Laakmann, Katrin Danov, Olga Limburg, Hannah Herbel, Stefanie Muriel Heimerl, Thomas Dorna, Jens Jonigk, Danny Preußer, Christian Bertrams, Wilhelm Braun, Armin Sewald, Katherina Schulte, Leon N. Bauer, Stefan Pogge von Strandmann, Elke Böttcher-Friebertshäuser, Eva Schmeck, Bernd Jung, Anna Lena Bacterial vesicles block viral replication in macrophages via TLR4-TRIF-axis |
title | Bacterial vesicles block viral replication in macrophages via TLR4-TRIF-axis |
title_full | Bacterial vesicles block viral replication in macrophages via TLR4-TRIF-axis |
title_fullStr | Bacterial vesicles block viral replication in macrophages via TLR4-TRIF-axis |
title_full_unstemmed | Bacterial vesicles block viral replication in macrophages via TLR4-TRIF-axis |
title_short | Bacterial vesicles block viral replication in macrophages via TLR4-TRIF-axis |
title_sort | bacterial vesicles block viral replication in macrophages via tlr4-trif-axis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045439/ https://www.ncbi.nlm.nih.gov/pubmed/36978183 http://dx.doi.org/10.1186/s12964-023-01086-4 |
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