Abstract
Major traumatic and surgical injury increase the risk for infectious complications due to immune dysregulation. Upon stimulation with interleukin (IL) 12 by monocyte/macrophages, natural killer (NK) cells release interferon (IFN) γ that supports the elimination of the pathogen. In the present study, we investigated the impact of invasive spine surgery on the relationship between monocytes and NK cells upon exposure to Staphylococcus aureus. Mononuclear cells and serum were isolated from peripheral blood of patients before and up to 8 d after surgery and stimulated with inactivated S. aureus bacteria. NK cell and monocyte function were determined by flow cytometry. NK cells continuously lost their ability to produce IFN-γ during the first week after surgery independently from monocyte-derived IL-12 secretion. IFN-γ synthesis was minimal on day 8 and was associated with decreased expression of the IL-12 receptor and activation of transcription factors required for IFNG gene transcription. Addition of recombinant IL-12 could at least partially restore NK cell function. Pre-operative levels of growth/differentiation factor (GDF) 15 in the serum correlated with the extent of NK cell suppression and with hospitalization. Thus, NK cell suppression after major surgery might represent a therapeutic target to improve the immune defense against opportunistic infections.
Highlights
Major traumatic or surgical tissue damage causes a dysregulation of the immune system and is associated with an increased risk for infectious complications [1]
There exists a cross-talk between monocytes/macrophages/dendritic cells (DCs) and natural killer (NK) cells based on the positive feedback loop between
We identified one of these factors as growth/differentiation factor (GDF) 15, a member of the TGF-β family that is produced at extremely high levels after trauma especially in those patients who later develop a septic complication [13]
Summary
Major traumatic or surgical tissue damage causes a dysregulation of the immune system and is associated with an increased risk for infectious complications [1]. Human circulating NK cells consist of two major subpopulations: CD56dim NK cells primarily act as cytotoxic effector cells that eliminate tumor cells and virus-infected cells and only weakly secrete cytokines [2]. CD56bright NK cells possess weak cytotoxic activity but release considerable amounts of diverse cytokines [3]. NK cells are a major source of IFN-γ that promotes the antimicrobial activity of macrophages and dendritic cells (DCs) [2,3,4]. Interleukin (IL) 12 is released by monocytes/macrophages and DCs upon contact with pathogen-derived components and activates NK cells for IFN-γ synthesis [5,6]. There exists a cross-talk between monocytes/macrophages/DCs and NK cells based on the positive feedback loop between
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