Invasive Surgery Impairs The Regulatory Function Of Human Cd56(Bright) Natural Killer Cells In Response To Staphylococcus Aureus. Suppression Of Interferon-Gamma Synthesis

Major surgery increases the risk for infectious complications due to the development of immunosuppression. CD56(bright) NK cells play a key role in the defense against bacterial infections through the release of Interferon (IFN) gamma upon stimulation with monocyte-derived Interleukin (IL) 12. We investigated whether invasive visceral surgery interferes with the IFN-gamma 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-gamma from PBMC upon exposure to S. aureus in vitro was quantified. The expression of the IL-12 receptor beta 1 chain on the surface, the phosphorylation of signal transducer and activator of transcription (STAT) 4, and the synthesis of IFN-gamma on/in individual CD56(bright) NK cells were investigated using flow cytometry. The modulatory effect of IL-12 on the S. aureus-induced IFN-gamma production in CD56(bright) NK cells was analyzed. The IFN-gamma secretion from purified CD56(bright) NK cells was quantified after stimulation with IL-12 and IL-18. After surgery, CD56(bright) NK cells among total PBMC were impaired in the release of IFN-gamma for at least 5 d. Likewise, the IL-12-induced release of IFN-gamma from purified CD56(bright) 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 CD56(bright) NK cells to produce IFN-gamma. CD56(bright) NK cells displayed reduced levels of the IL-12R beta 1 chain whereas the phosphorylation of STAT4, the key transcription factor for the Ifng gene was not diminished. In summary, after invasive visceral surgery, CD56(bright) NK cells are impaired in S. aureus-induced IFN-gamma production and might contribute to the enhanced susceptibility to opportunistic infections.