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Staphylococcus aureus Lung Infection Results in Down-Regulation of Surfactant Protein-A Mainly Caused by Pro-Inflammatory Macrophages

Pneumonia is the leading cause of hospitalization worldwide. Besides viruses, bacterial co-infections dramatically exacerbate infection. In general, surfactant protein-A (SP-A) represents a first line of immune defense. In this study, we analyzed whether influenza A virus (IAV) and/or Staphylococcus...

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Autores principales: Schicke, Elisabeth, Cseresnyés, Zoltán, Rennert, Knut, Vau, Vanessa, Haupt, Karoline Frieda, Hornung, Franziska, Nietzsche, Sandor, Swiczak, Fatina, Schmidtke, Michaela, Glück, Brigitte, Koch, Mirijam, Schacke, Michael, Heller, Regine, Mosig, Alexander S., Figge, Marc Thilo, Ehrhardt, Christina, Löffler, Bettina, Deinhardt-Emmer, Stefanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232181/
https://www.ncbi.nlm.nih.gov/pubmed/32316261
http://dx.doi.org/10.3390/microorganisms8040577
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author Schicke, Elisabeth
Cseresnyés, Zoltán
Rennert, Knut
Vau, Vanessa
Haupt, Karoline Frieda
Hornung, Franziska
Nietzsche, Sandor
Swiczak, Fatina
Schmidtke, Michaela
Glück, Brigitte
Koch, Mirijam
Schacke, Michael
Heller, Regine
Mosig, Alexander S.
Figge, Marc Thilo
Ehrhardt, Christina
Löffler, Bettina
Deinhardt-Emmer, Stefanie
author_facet Schicke, Elisabeth
Cseresnyés, Zoltán
Rennert, Knut
Vau, Vanessa
Haupt, Karoline Frieda
Hornung, Franziska
Nietzsche, Sandor
Swiczak, Fatina
Schmidtke, Michaela
Glück, Brigitte
Koch, Mirijam
Schacke, Michael
Heller, Regine
Mosig, Alexander S.
Figge, Marc Thilo
Ehrhardt, Christina
Löffler, Bettina
Deinhardt-Emmer, Stefanie
author_sort Schicke, Elisabeth
collection PubMed
description Pneumonia is the leading cause of hospitalization worldwide. Besides viruses, bacterial co-infections dramatically exacerbate infection. In general, surfactant protein-A (SP-A) represents a first line of immune defense. In this study, we analyzed whether influenza A virus (IAV) and/or Staphylococcus aureus (S. aureus) infections affect SP-A expression. To closely reflect the situation in the lung, we used a human alveolus-on-a-chip model and a murine pneumonia model. Our results show that S. aureus can reduce extracellular levels of SP-A, most likely attributed to bacterial proteases. Mono-epithelial cell culture experiments reveal that the expression of SP-A is not directly affected by IAV or S. aureus. Yet, the mRNA expression of SP-A is strongly down-regulated by TNF-α, which is highly produced by professional phagocytes in response to bacterial infection. By using the human alveolus-on-a-chip model, we show that the down-regulation of SP-A is strongly dependent on macrophages. In a murine model of pneumonia, we can confirm that S. aureus decreases SP-A levels in vivo. These findings indicate that (I) complex interactions of epithelial and immune cells induce down-regulation of SP-A expression and (II) bacterial mono- and super-infections reduce SP-A expression in the lung, which might contribute to a severe outcome of bacterial pneumonia.
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spelling pubmed-72321812020-05-22 Staphylococcus aureus Lung Infection Results in Down-Regulation of Surfactant Protein-A Mainly Caused by Pro-Inflammatory Macrophages Schicke, Elisabeth Cseresnyés, Zoltán Rennert, Knut Vau, Vanessa Haupt, Karoline Frieda Hornung, Franziska Nietzsche, Sandor Swiczak, Fatina Schmidtke, Michaela Glück, Brigitte Koch, Mirijam Schacke, Michael Heller, Regine Mosig, Alexander S. Figge, Marc Thilo Ehrhardt, Christina Löffler, Bettina Deinhardt-Emmer, Stefanie Microorganisms Article Pneumonia is the leading cause of hospitalization worldwide. Besides viruses, bacterial co-infections dramatically exacerbate infection. In general, surfactant protein-A (SP-A) represents a first line of immune defense. In this study, we analyzed whether influenza A virus (IAV) and/or Staphylococcus aureus (S. aureus) infections affect SP-A expression. To closely reflect the situation in the lung, we used a human alveolus-on-a-chip model and a murine pneumonia model. Our results show that S. aureus can reduce extracellular levels of SP-A, most likely attributed to bacterial proteases. Mono-epithelial cell culture experiments reveal that the expression of SP-A is not directly affected by IAV or S. aureus. Yet, the mRNA expression of SP-A is strongly down-regulated by TNF-α, which is highly produced by professional phagocytes in response to bacterial infection. By using the human alveolus-on-a-chip model, we show that the down-regulation of SP-A is strongly dependent on macrophages. In a murine model of pneumonia, we can confirm that S. aureus decreases SP-A levels in vivo. These findings indicate that (I) complex interactions of epithelial and immune cells induce down-regulation of SP-A expression and (II) bacterial mono- and super-infections reduce SP-A expression in the lung, which might contribute to a severe outcome of bacterial pneumonia. MDPI 2020-04-16 /pmc/articles/PMC7232181/ /pubmed/32316261 http://dx.doi.org/10.3390/microorganisms8040577 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schicke, Elisabeth
Cseresnyés, Zoltán
Rennert, Knut
Vau, Vanessa
Haupt, Karoline Frieda
Hornung, Franziska
Nietzsche, Sandor
Swiczak, Fatina
Schmidtke, Michaela
Glück, Brigitte
Koch, Mirijam
Schacke, Michael
Heller, Regine
Mosig, Alexander S.
Figge, Marc Thilo
Ehrhardt, Christina
Löffler, Bettina
Deinhardt-Emmer, Stefanie
Staphylococcus aureus Lung Infection Results in Down-Regulation of Surfactant Protein-A Mainly Caused by Pro-Inflammatory Macrophages
title Staphylococcus aureus Lung Infection Results in Down-Regulation of Surfactant Protein-A Mainly Caused by Pro-Inflammatory Macrophages
title_full Staphylococcus aureus Lung Infection Results in Down-Regulation of Surfactant Protein-A Mainly Caused by Pro-Inflammatory Macrophages
title_fullStr Staphylococcus aureus Lung Infection Results in Down-Regulation of Surfactant Protein-A Mainly Caused by Pro-Inflammatory Macrophages
title_full_unstemmed Staphylococcus aureus Lung Infection Results in Down-Regulation of Surfactant Protein-A Mainly Caused by Pro-Inflammatory Macrophages
title_short Staphylococcus aureus Lung Infection Results in Down-Regulation of Surfactant Protein-A Mainly Caused by Pro-Inflammatory Macrophages
title_sort staphylococcus aureus lung infection results in down-regulation of surfactant protein-a mainly caused by pro-inflammatory macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232181/
https://www.ncbi.nlm.nih.gov/pubmed/32316261
http://dx.doi.org/10.3390/microorganisms8040577
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