title: A disturbed interaction with accessory cells upon opportunistic infection with Pseudomonas aeruginosa contributes to an impaired IFN-γ production of NK cells in the lung during sepsis-induced immunosuppression.
abstract: Impaired resistance to Pseudomonas aeruginosa-induced pneumonia after cecal ligation and puncture (CLP), a mouse model for human polymicrobial sepsis, is associated with decreased IFN-γ, but increased IL-10, levels in the lung. We investigated the so far unknown mechanisms underlying this reduced IFN-γ synthesis in CLP mice. CD11b(+) NK cells, but not T or NKT cells in the lung were impaired in IFN-γ synthesis upon challenge with Pseudomonas in vitro and in vivo after CLP. The inhibition of NK cells was independent of IL-10. IFN-γ synthesis of NK cells was only partly restored by addition of recombinant IL-12. Accessory cells including dendritic cells and alveolar macrophages were required for maximal IFN-γ secretion. But accessory cells of CLP mice suppressed the IFN-γ secretion from naive lung leukocytes. In turn, naive accessory cells were unable to restore the IFN-γ production from lung leukocytes of CLP mice. Thus, a disturbed interaction of accessory cells and NK cells is involved in the impaired IFN-γ release in response to Pseudomonas in the lung of CLP mice. Considering the importance of IFN-γ in the immune defense against bacteria the dysfunction of accessory cells and NK cells might contribute to the enhanced susceptibility to Pseudomonas after CLP.
authors.affiliation: Surgical Research, Department of Trauma Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany Institute for Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Pastille
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 Institute of Cell Biology (Cancer Research), Medical School, University Duisburg-Essen, Essen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Wirsdörfer
authors.affiliation: Surgical Research, Department of Trauma Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Reib
authors.affiliation: Surgical Research, Department of Trauma Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany stefanie.flohe@uk-essen.de.
authors.forename: Stefanie B
authors.initials: SB
authors.lastname: Flohé
mesh_terms: D000818:Animals; D002432:Cecum / Q000601:surgery; D002450:Cell Communication; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009894:Opportunistic Infections / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D018805:Sepsis / Q000276:immunology*
chemical_list: D007371:Interferon-gamma
keywords: NK cells; Pseudomonas; Sepsis; dendritic cells; immunosuppression; macrophages