IL-15 promotes polyfunctional NK cell responses to influenza by boosting IL-12 production
IL-15 is a key regulator of NK cell maintenance and proliferation and synergizes with other myeloid cell–derived cytokines to enhance NK cell effector function. At low concentrations, trans-presentation of IL-15 by dendritic cells can activate NK cells, whereas at higher concentrations it can act di...
| Main Authors: | , , , |
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| Format: | Journal article |
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American Association of Immunologists
2018
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| _version_ | 1797091213367574528 |
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| author | Wagstaffe, HR Nielsen, CM Riley, EM Goodier, MR |
| author_facet | Wagstaffe, HR Nielsen, CM Riley, EM Goodier, MR |
| author_sort | Wagstaffe, HR |
| collection | OXFORD |
| description | IL-15 is a key regulator of NK cell maintenance and proliferation and synergizes with other myeloid cell–derived cytokines to enhance NK cell effector function. At low concentrations, trans-presentation of IL-15 by dendritic cells can activate NK cells, whereas at higher concentrations it can act directly on NK cells, independently of accessory cells. In this study, we investigate the potential for IL-15 to boost responses to influenza virus by promoting accessory cell function. We find that coculture of human PBMCs with inactivated whole influenza virus (A/Victoria/361/2011) in the presence of very low concentrations of IL-15 results in increased production of myeloid cell–derived cytokines, including IL-12, IFN-α2, GM-CSF, and IL-1β, and an increased frequency of polyfunctional NK cells (defined by the expression of two or more of CD107a, IFN-γ, and CD25). Neutralization experiments demonstrate that IL-15–mediated enhancement of NK cell responses is primarily dependent on IL-12 and partially dependent on IFN-αβR1 signaling. Critically, IL-15 boosted the production of IL-12 in influenza-stimulated blood myeloid dendritic cells. IL-15 costimulation also restored the ability of less-differentiated NK cells from human CMV-seropositive individuals to respond to influenza virus. These data suggest that very low concentrations of IL-15 play an important role in boosting accessory cell function to support NK cell effector functions. |
| first_indexed | 2024-03-07T03:29:46Z |
| format | Journal article |
| id | oxford-uuid:ba4e80af-0bc9-4869-80c7-5a48f4b174ae |
| institution | University of Oxford |
| last_indexed | 2024-03-07T03:29:46Z |
| publishDate | 2018 |
| publisher | American Association of Immunologists |
| record_format | dspace |
| spelling | oxford-uuid:ba4e80af-0bc9-4869-80c7-5a48f4b174ae2022-03-27T05:08:59ZIL-15 promotes polyfunctional NK cell responses to influenza by boosting IL-12 productionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ba4e80af-0bc9-4869-80c7-5a48f4b174aeSymplectic Elements at OxfordAmerican Association of Immunologists2018Wagstaffe, HRNielsen, CMRiley, EMGoodier, MRIL-15 is a key regulator of NK cell maintenance and proliferation and synergizes with other myeloid cell–derived cytokines to enhance NK cell effector function. At low concentrations, trans-presentation of IL-15 by dendritic cells can activate NK cells, whereas at higher concentrations it can act directly on NK cells, independently of accessory cells. In this study, we investigate the potential for IL-15 to boost responses to influenza virus by promoting accessory cell function. We find that coculture of human PBMCs with inactivated whole influenza virus (A/Victoria/361/2011) in the presence of very low concentrations of IL-15 results in increased production of myeloid cell–derived cytokines, including IL-12, IFN-α2, GM-CSF, and IL-1β, and an increased frequency of polyfunctional NK cells (defined by the expression of two or more of CD107a, IFN-γ, and CD25). Neutralization experiments demonstrate that IL-15–mediated enhancement of NK cell responses is primarily dependent on IL-12 and partially dependent on IFN-αβR1 signaling. Critically, IL-15 boosted the production of IL-12 in influenza-stimulated blood myeloid dendritic cells. IL-15 costimulation also restored the ability of less-differentiated NK cells from human CMV-seropositive individuals to respond to influenza virus. These data suggest that very low concentrations of IL-15 play an important role in boosting accessory cell function to support NK cell effector functions. |
| spellingShingle | Wagstaffe, HR Nielsen, CM Riley, EM Goodier, MR IL-15 promotes polyfunctional NK cell responses to influenza by boosting IL-12 production |
| title | IL-15 promotes polyfunctional NK cell responses to influenza by boosting IL-12 production |
| title_full | IL-15 promotes polyfunctional NK cell responses to influenza by boosting IL-12 production |
| title_fullStr | IL-15 promotes polyfunctional NK cell responses to influenza by boosting IL-12 production |
| title_full_unstemmed | IL-15 promotes polyfunctional NK cell responses to influenza by boosting IL-12 production |
| title_short | IL-15 promotes polyfunctional NK cell responses to influenza by boosting IL-12 production |
| title_sort | il 15 promotes polyfunctional nk cell responses to influenza by boosting il 12 production |
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