Abstract
Major surgery increases the risk for infectious complications due to the development of immunosuppression. CD56bright NK cells play a key role in the defense against bacterial infections through the release of Interferon (IFN) γ upon stimulation with monocyte-derived Interleukin (IL) 12. We investigated whether invasive visceral surgery interferes with the IFN-γ synthesis of human NK cells in response to Staphylococcus aureus. In a prospective pilot study, peripheral blood mononuclear cells (PBMC) were isolated from 53 patients before and 1 to 7 d after elective visceral surgery. The release of IL-12 and IFN-γ from PBMC upon exposure to S. aureus in vitro was quantified. The expression of the IL-12 receptor β1 chain on the surface, the phosphorylation of signal transducer and activator of transcription (STAT) 4, and the synthesis of IFN-γ on/in individual CD56bright NK cells were investigated using flow cytometry. The modulatory effect of IL-12 on the S. aureus-induced IFN-γ production in CD56bright NK cells was analyzed. The IFN-γ secretion from purified CD56bright NK cells was quantified after stimulation with IL-12 and IL-18. After surgery, CD56bright NK cells among total PBMC were impaired in the release of IFN-γ for at least 5 d. Likewise, the IL-12-induced release of IFN-γ from purified CD56bright NK cells was abolished. Upon stimulation with S. aureus, PBMC secreted less IL-12 but supplementation with recombinant IL-12 did not restore the capacity of CD56bright NK cells to produce IFN-γ. CD56bright NK cells displayed reduced levels of the IL-12Rβ1 chain whereas the phosphorylation of STAT4, the key transcription factor for the Ifng gene was not diminished. In summary, after invasive visceral surgery, CD56bright NK cells are impaired in S. aureus-induced IFN-γ production and might contribute to the enhanced susceptibility to opportunistic infections.
Highlights
After major surgery and severe injury patients often experience infectious complications due to the development of immunosuppression [1]
We examined whether the reduced release of S. aureus-induced IFN-γ from peripheral blood mononuclear cells (PBMC) after surgery originated in a decreased percentage of CD56bright natural killer (NK) cells among total PBMC
Downstream of the IL-12 receptor (IL-12R), we evaluated whether the phosphorylation of STAT4, the key transcription factor for transcription of the Ifng gene changed in CD56bright NK cells upon injury
Summary
After major surgery and severe injury patients often experience infectious complications due to the development of immunosuppression [1]. Monocyte deactivation that is characterized by a reduced expression of HLA-DR molecules on the surface and a decreased release of tumornecrosis factor (TNF) α and Interleukin (IL) 12 in response to microbial stimulation is considered to contribute to immunoparalysis after severe injury [2,3,4]. The successful elimination of bacteria requires the activity of cells of the innate immune system such as macrophages and neutrophilic granulocytes that ingest and eradicate microorganisms and subsequently clear the infection. IL-12 activates natural killer (NK) cells for the release of Interferon (IFN) γ that in turn increases the bactericidal activity of macrophages [5]. The IL-12/IFN-γ axis plays an important role in the defense against bacterial infections
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