title: Invasive Surgery Impairs the Regulatory Function of Human CD56 bright Natural Killer Cells in Response to Staphylococcus aureus. Suppression of Interferon-γ Synthesis.
abstract: 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) 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 CD56 bright NK cells were investigated using flow cytometry. The modulatory effect of IL-12 on the S. aureus-induced IFN-γ production in CD56 bright NK cells was analyzed. The IFN-γ 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-γ for at least 5 d. Likewise, the IL-12-induced release of IFN-γ 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-γ. CD56 bright 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, CD56 bright NK cells are impaired in S. aureus-induced IFN-γ production and might contribute to the enhanced susceptibility to opportunistic infections.
authors.affiliation: Department of General-, Visceral- and Transplantation Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Renate
authors.initials: R
authors.lastname: Reinhardt
authors.affiliation: Surgical Research, Department of Trauma Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Pohlmann
authors.affiliation: Surgical Research, Department of Trauma Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Kleinertz
authors.affiliation: Surgical Research, Department of Trauma Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Hepner-Schefczyk
authors.affiliation: Department of General-, Visceral- and Transplantation Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Paul
authors.affiliation: Surgical Research, Department of Trauma Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Stefanie B
authors.initials: SB
authors.lastname: Flohé
mesh_terms: D000368:Aged; D019002:CD56 Antigen / Q000378:metabolism; D005260:Female; D006801:Humans; D056747:Immunomodulation; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D053707:Receptors, Interleukin-12 / Q000378:metabolism; D050797:STAT4 Transcription Factor / Q000378:metabolism; D013203:Staphylococcal Infections / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology*; D013514:Surgical Procedures, Operative / Q000009:adverse effects*
chemical_list: D019002:CD56 Antigen; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; D018664:Interleukin-12; D007371:Interferon-gamma