Circulating growth/differentiation factor 15 is associated with human CD56
Adult
Biomarkers
CD56 Antigen
/ metabolism
Comorbidity
Cross Infection
/ blood
Female
Growth Differentiation Factor 15
/ blood
Humans
Immunophenotyping
Inflammation Mediators
/ metabolism
Interferon-gamma
/ metabolism
Interleukin-12
/ metabolism
Killer Cells, Natural
/ immunology
Male
Middle Aged
Phosphorylation
Receptors, Interleukin-12
/ metabolism
STAT4 Transcription Factor
/ metabolism
Severity of Illness Index
Signal Transduction
Systemic Inflammatory Response Syndrome
/ blood
Immunosuppression
Interferon gamma
Interleukin 12
Natural killer cells
Opportunistic infections
Transforming growth factor receptor
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
May 2019
May 2019
Historique:
received:
14
01
2019
revised:
18
03
2019
accepted:
08
04
2019
pubmed:
18
4
2019
medline:
26
11
2019
entrez:
18
4
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
RESULTS
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
CONCLUSIONS
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.
Identifiants
pubmed: 30992245
pii: S2352-3964(19)30252-X
doi: 10.1016/j.ebiom.2019.04.018
pmc: PMC6557805
pii:
doi:
Substances chimiques
Biomarkers
0
CD56 Antigen
0
GDF15 protein, human
0
Growth Differentiation Factor 15
0
Inflammation Mediators
0
NCAM1 protein, human
0
Receptors, Interleukin-12
0
STAT4 Transcription Factor
0
Interleukin-12
187348-17-0
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
380-391Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
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