IL-15 Promotes Polyfunctional NK Cell Responses to Influenza by Boosting IL-12 Production

The Journal of Immunology : Official Journal of the American Association of Immunologists
Helen R WagstaffeMartin R Goodier

Abstract

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-seropos...Continue Reading

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Citations

Aug 21, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Helen R WagstaffeMartin R Goodier
Dec 11, 2019·The Journal of Infectious Diseases·Helen R WagstaffeMartin R Goodier
May 7, 2019·Frontiers in Immunology·Jacqueline M CliffEleanor M Riley
Jun 9, 2020·Frontiers in Cellular and Infection Microbiology·Stephen PierceTodd Bradley
Dec 3, 2020·Frontiers of Medicine·Qian XuGang Huang
Jan 29, 2021·Clinical & Translational Immunology·Martin R Goodier, Eleanor M Riley
Mar 17, 2019·Current Opinion in Virology·Ayad AliStephen N Waggoner

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
ELISA
Flow
FACS
flow cytometry

Software Mentioned

SPICE
Plex
Bio
FlowJo
GraphPad Prism
FACSDiva

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