Adaptive Natural Killer Cells Integrate Interleukin-18 during Target-Cell Encounter
Human cytomegalovirus (HCMV) infection induces adaptations in the natural killer (NK)-cell compartment. Expanded subsets of adaptive NK cells display potent effector functions against cellular targets, despite their apparent unresponsiveness to stimulation with classical dendritic cell-derived cytok...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-01-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01976/full |
| _version_ | 1818530034062721024 |
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| author | Quirin Hammer Timo Rückert Josefine Dunst Chiara Romagnani Chiara Romagnani |
| author_facet | Quirin Hammer Timo Rückert Josefine Dunst Chiara Romagnani Chiara Romagnani |
| author_sort | Quirin Hammer |
| collection | DOAJ |
| description | Human cytomegalovirus (HCMV) infection induces adaptations in the natural killer (NK)-cell compartment. Expanded subsets of adaptive NK cells display potent effector functions against cellular targets, despite their apparent unresponsiveness to stimulation with classical dendritic cell-derived cytokines interleukin (IL)-12 and IL-18. However, it remains unclear whether adaptive NK cells have completely lost their ability to sense inflammation via IL-12 and IL-18 or whether these pro-inflammatory signals can be functionally integrated into defined contexts. Here, we demonstrate that adaptive NKG2C+ NK cells can be costimulated by the presence of pro-inflammatory cytokines during target cell-induced activation. Cytokine costimulation of adaptive NK cells resulted in elevated interferon (IFN)-gamma and tumor necrosis factor (TNF) production, which promoted protein expression of HLA class I and adhesion molecules as well as transcription of genes involved in antigen processing and antiviral states in endothelial bystander cells in vitro. We further show that IL-18 drove costimulation in functional assays and was sufficient for elevated cytokine production in the absence of IL-12. Hence, adaptive NKG2C+ NK cells—although poorly responsive to IL-12 and IL-18 as an isolated stimulus—integrate IL-18 as a costimulatory signal during target-cell encounter. |
| first_indexed | 2024-12-11T17:14:37Z |
| format | Article |
| id | doaj.art-65aa65727a094470a651595f3944f57c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T17:14:37Z |
| publishDate | 2018-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-65aa65727a094470a651595f3944f57c2022-12-22T00:57:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-01-01810.3389/fimmu.2017.01976323365Adaptive Natural Killer Cells Integrate Interleukin-18 during Target-Cell EncounterQuirin Hammer0Timo Rückert1Josefine Dunst2Chiara Romagnani3Chiara Romagnani4Innate Immunity, German Rheumatism Research Center (DRFZ), Leibniz Association, Berlin, GermanyInnate Immunity, German Rheumatism Research Center (DRFZ), Leibniz Association, Berlin, GermanyInflammation Biology, German Rheumatism Research Center (DRFZ), Leibniz Association, Berlin, GermanyInnate Immunity, German Rheumatism Research Center (DRFZ), Leibniz Association, Berlin, GermanyMedical Department I, Charité – University Medicine Berlin, Berlin, GermanyHuman cytomegalovirus (HCMV) infection induces adaptations in the natural killer (NK)-cell compartment. Expanded subsets of adaptive NK cells display potent effector functions against cellular targets, despite their apparent unresponsiveness to stimulation with classical dendritic cell-derived cytokines interleukin (IL)-12 and IL-18. However, it remains unclear whether adaptive NK cells have completely lost their ability to sense inflammation via IL-12 and IL-18 or whether these pro-inflammatory signals can be functionally integrated into defined contexts. Here, we demonstrate that adaptive NKG2C+ NK cells can be costimulated by the presence of pro-inflammatory cytokines during target cell-induced activation. Cytokine costimulation of adaptive NK cells resulted in elevated interferon (IFN)-gamma and tumor necrosis factor (TNF) production, which promoted protein expression of HLA class I and adhesion molecules as well as transcription of genes involved in antigen processing and antiviral states in endothelial bystander cells in vitro. We further show that IL-18 drove costimulation in functional assays and was sufficient for elevated cytokine production in the absence of IL-12. Hence, adaptive NKG2C+ NK cells—although poorly responsive to IL-12 and IL-18 as an isolated stimulus—integrate IL-18 as a costimulatory signal during target-cell encounter.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01976/fullhuman natural killer cellsadaptive natural killer cellsNKG2Cinterleukin-18costimulation |
| spellingShingle | Quirin Hammer Timo Rückert Josefine Dunst Chiara Romagnani Chiara Romagnani Adaptive Natural Killer Cells Integrate Interleukin-18 during Target-Cell Encounter Frontiers in Immunology human natural killer cells adaptive natural killer cells NKG2C interleukin-18 costimulation |
| title | Adaptive Natural Killer Cells Integrate Interleukin-18 during Target-Cell Encounter |
| title_full | Adaptive Natural Killer Cells Integrate Interleukin-18 during Target-Cell Encounter |
| title_fullStr | Adaptive Natural Killer Cells Integrate Interleukin-18 during Target-Cell Encounter |
| title_full_unstemmed | Adaptive Natural Killer Cells Integrate Interleukin-18 during Target-Cell Encounter |
| title_short | Adaptive Natural Killer Cells Integrate Interleukin-18 during Target-Cell Encounter |
| title_sort | adaptive natural killer cells integrate interleukin 18 during target cell encounter |
| topic | human natural killer cells adaptive natural killer cells NKG2C interleukin-18 costimulation |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01976/full |
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