Influenza infection enhances antibody-mediated NK cell functions via Type I interferon dependent pathways

Jegaskanda, Sinthujan, Vanderven, Hillary A., Tan, Hyon-Xhi, Alcantara, Sheilajen, Wragg, Kathleen, Parsons, Matthew S., Chung, Amy, Juno, Jennifer A., and Kent, Stephen J. (2018) Influenza infection enhances antibody-mediated NK cell functions via Type I interferon dependent pathways. Journal of Virology, 9 (5). 02090-18.

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Abstract

NK cells are an important component in the control of influenza infection, acting to both clear virus-infected cells and release antiviral cytokines. Engagement of CD16 on NK cells by antibody-coated influenza-infected cells results in antibody-dependent cellular cytotoxicity (ADCC). Increasing the potency of antibody-mediated NK cell activity could ultimately lead to improved control of influenza infection. To understand if NK cells can be functionally enhanced following exposure to influenza virus-infected cells, we co-cultured human PBMCs with influenza-infected human alveolar epithelial (A549) cells and evaluated the capacity of NK cells to mediate antibody-dependent functions. Pre-incubation of PBMCs with influenza-infected cells markedly enhanced the ability of NK cells to respond to immune complexes containing HA and anti-HA antibodies or transformed allogenic cells in the presence or absence of a therapeutic monoclonal antibody. Cytokine multiplex, RNA sequencing, supernatant transfer, trans-well and cytokine blocking/supplementation experiments showed that type I interferons released from PBMCs were primarily responsible for the influenza-induced enhancement of antibody-mediated NK cell functions. Importantly, the influenza-mediated increase in antibody-dependent NK cell functionality was mimicked by the type I interferon agonist poly(I:C). We conclude that type I interferon secretion induced by influenza virus infection enhances the capacity of NK cells to mediate ADCC, and this pathway could be manipulated to alter the potency of anti-influenza therapies and vaccines.

Item ID: 56937
Item Type: Article (Research - C1)
ISSN: 1098-5514
Copyright Information: Copyright © 2018 American Society for Microbiology. All Rights Reserved.
Funders: National Health and Medical Research Council of Australia (NHMRC)
Date Deposited: 21 Aug 2019 01:03
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
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