RESEARCH ARTICLE Invasive Surgery Impairs the Regulatory Function of Human CD56bright Natural Killer Cells in Response to Staphylococcus aureus. Suppression of Interferon-γ Synthesis

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