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Circulating growth/differentiation factor 15 is associated with human CD56(bright) natural killer cell dysfunction and nosocomial infection in severe systemic inflammation

BACKGROUND: Systemic inflammation induced by sterile or infectious insults is associated with an enhanced susceptibility to life-threatening opportunistic, mostly bacterial, infections due to unknown pathogenesis. Natural killer (NK) cells contribute to the defence against bacterial infections throu...

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Autores principales: Kleinertz, Holger, Hepner-Schefczyk, Monika, Ehnert, Sabrina, Claus, Maren, Halbgebauer, Rebecca, Boller, Lea, Huber-Lang, Markus, Cinelli, Paolo, Kirschning, Carsten, Flohé, Sascha, Sander, André, Waydhas, Christian, Vonderhagen, Sonja, Jäger, Marcus, Dudda, Marcel, Watzl, Carsten, Flohé, Stefanie B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557805/
https://www.ncbi.nlm.nih.gov/pubmed/30992245
http://dx.doi.org/10.1016/j.ebiom.2019.04.018
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author Kleinertz, Holger
Hepner-Schefczyk, Monika
Ehnert, Sabrina
Claus, Maren
Halbgebauer, Rebecca
Boller, Lea
Huber-Lang, Markus
Cinelli, Paolo
Kirschning, Carsten
Flohé, Sascha
Sander, André
Waydhas, Christian
Vonderhagen, Sonja
Jäger, Marcus
Dudda, Marcel
Watzl, Carsten
Flohé, Stefanie B.
author_facet Kleinertz, Holger
Hepner-Schefczyk, Monika
Ehnert, Sabrina
Claus, Maren
Halbgebauer, Rebecca
Boller, Lea
Huber-Lang, Markus
Cinelli, Paolo
Kirschning, Carsten
Flohé, Sascha
Sander, André
Waydhas, Christian
Vonderhagen, Sonja
Jäger, Marcus
Dudda, Marcel
Watzl, Carsten
Flohé, Stefanie B.
author_sort Kleinertz, Holger
collection PubMed
description BACKGROUND: Systemic inflammation induced by sterile or infectious insults is associated with an enhanced susceptibility to life-threatening opportunistic, mostly bacterial, infections due to unknown pathogenesis. Natural killer (NK) cells contribute to the defence against bacterial infections through the release of Interferon (IFN) γ in response to Interleukin (IL) 12. Considering the relevance of NK cells in the immune defence we investigated whether the function of NK cells is disturbed in patients suffering from serious systemic inflammation. METHODS: NK cells from severely injured patients were analysed from the first day after the initial inflammatory insult until the day of discharge in terms of IL-12 receptor signalling and IFN-γ synthesis. FINDINGS: During systemic inflammation, the expression of the IL-12 receptor β2 chain, phosphorylation of signal transducer and activation 4, and IFN-γ production on/in NK cells was impaired upon exposure to Staphylococcus aureus. The profound suppression of NK cells developed within 24 h after the initial insult and persisted for several weeks. NK cells displayed signs of exhaustion. Extrinsic changes were mediated by the early and long-lasting presence of growth/differentiation factor (GDF) 15 in the circulation that signalled through the transforming growth factor β receptor I and activated Smad1/5. Moreover, the concentration of GDF-15 in the serum inversely correlated with the IL-12 receptor β2 expression on NK cells and was enhanced in patients who later acquired septic complications. INTERPRETATION: GDF-15 is associated with the development of NK cell dysfunction during systemic inflammation and might represent a novel target to prevent nosocomial infections. FUND: The study was supported by the Department of Orthopaedics and Trauma Surgery, University Hospital Essen.
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spelling pubmed-65578052019-06-14 Circulating growth/differentiation factor 15 is associated with human CD56(bright) natural killer cell dysfunction and nosocomial infection in severe systemic inflammation Kleinertz, Holger Hepner-Schefczyk, Monika Ehnert, Sabrina Claus, Maren Halbgebauer, Rebecca Boller, Lea Huber-Lang, Markus Cinelli, Paolo Kirschning, Carsten Flohé, Sascha Sander, André Waydhas, Christian Vonderhagen, Sonja Jäger, Marcus Dudda, Marcel Watzl, Carsten Flohé, Stefanie B. EBioMedicine Research paper BACKGROUND: Systemic inflammation induced by sterile or infectious insults is associated with an enhanced susceptibility to life-threatening opportunistic, mostly bacterial, infections due to unknown pathogenesis. Natural killer (NK) cells contribute to the defence against bacterial infections through the release of Interferon (IFN) γ in response to Interleukin (IL) 12. Considering the relevance of NK cells in the immune defence we investigated whether the function of NK cells is disturbed in patients suffering from serious systemic inflammation. METHODS: NK cells from severely injured patients were analysed from the first day after the initial inflammatory insult until the day of discharge in terms of IL-12 receptor signalling and IFN-γ synthesis. FINDINGS: During systemic inflammation, the expression of the IL-12 receptor β2 chain, phosphorylation of signal transducer and activation 4, and IFN-γ production on/in NK cells was impaired upon exposure to Staphylococcus aureus. The profound suppression of NK cells developed within 24 h after the initial insult and persisted for several weeks. NK cells displayed signs of exhaustion. Extrinsic changes were mediated by the early and long-lasting presence of growth/differentiation factor (GDF) 15 in the circulation that signalled through the transforming growth factor β receptor I and activated Smad1/5. Moreover, the concentration of GDF-15 in the serum inversely correlated with the IL-12 receptor β2 expression on NK cells and was enhanced in patients who later acquired septic complications. INTERPRETATION: GDF-15 is associated with the development of NK cell dysfunction during systemic inflammation and might represent a novel target to prevent nosocomial infections. FUND: The study was supported by the Department of Orthopaedics and Trauma Surgery, University Hospital Essen. Elsevier 2019-04-13 /pmc/articles/PMC6557805/ /pubmed/30992245 http://dx.doi.org/10.1016/j.ebiom.2019.04.018 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research paper
Kleinertz, Holger
Hepner-Schefczyk, Monika
Ehnert, Sabrina
Claus, Maren
Halbgebauer, Rebecca
Boller, Lea
Huber-Lang, Markus
Cinelli, Paolo
Kirschning, Carsten
Flohé, Sascha
Sander, André
Waydhas, Christian
Vonderhagen, Sonja
Jäger, Marcus
Dudda, Marcel
Watzl, Carsten
Flohé, Stefanie B.
Circulating growth/differentiation factor 15 is associated with human CD56(bright) natural killer cell dysfunction and nosocomial infection in severe systemic inflammation
title Circulating growth/differentiation factor 15 is associated with human CD56(bright) natural killer cell dysfunction and nosocomial infection in severe systemic inflammation
title_full Circulating growth/differentiation factor 15 is associated with human CD56(bright) natural killer cell dysfunction and nosocomial infection in severe systemic inflammation
title_fullStr Circulating growth/differentiation factor 15 is associated with human CD56(bright) natural killer cell dysfunction and nosocomial infection in severe systemic inflammation
title_full_unstemmed Circulating growth/differentiation factor 15 is associated with human CD56(bright) natural killer cell dysfunction and nosocomial infection in severe systemic inflammation
title_short Circulating growth/differentiation factor 15 is associated with human CD56(bright) natural killer cell dysfunction and nosocomial infection in severe systemic inflammation
title_sort circulating growth/differentiation factor 15 is associated with human cd56(bright) natural killer cell dysfunction and nosocomial infection in severe systemic inflammation
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557805/
https://www.ncbi.nlm.nih.gov/pubmed/30992245
http://dx.doi.org/10.1016/j.ebiom.2019.04.018
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