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Influenza Virus Infection Enhances Antibody-Mediated NK Cell Functions via Type I Interferon-Dependent Pathways.

Abstract：

:Natural killer (NK) cells are an important component in the control of influenza virus infection, acting to both clear virus-infected cells and release antiviral cytokines. Engagement of CD16 on NK cells by antibody-coated influenza virus-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 virus infection. To understand if NK cells can be functionally enhanced following exposure to influenza virus-infected cells, we cocultured human peripheral blood mononuclear cells (PBMCs) with influenza virus-infected human alveolar epithelial (A549) cells and evaluated the capacity of NK cells to mediate antibody-dependent functions. Preincubation of PBMCs with influenza virus-infected cells markedly enhanced the ability of NK cells to respond to immune complexes containing hemagglutinin (HA) and anti-HA antibodies or transformed allogeneic cells in the presence or absence of a therapeutic monoclonal antibody. Cytokine multiplex, RNA sequencing, supernatant transfer, Transwell, and cytokine-blocking/cytokine supplementation experiments showed that type I interferons released from PBMCs were primarily responsible for the influenza virus-induced enhancement of antibody-mediated NK cell functions. Importantly, the influenza virus-mediated increase in antibody-dependent NK cell functionality was mimicked by the type I interferon agonist poly(I·C). We conclude that the type I interferon secretion induced by influenza virus infection enhances the capacity of NK cells to mediate ADCC and that this pathway could be manipulated to alter the potency of anti-influenza virus therapies and vaccines.IMPORTANCE Protection from severe influenza may be assisted by antibodies that engage NK cells to kill infected cells through ADCC. Studies have primarily focused on antibodies that have ADCC activity, rather than the capacity of NK cells to become activated and mediate ADCC during an influenza virus infection. We found that type I interferon released in response to influenza virus infection primes NK cells to become highly reactive to anti-influenza virus ADCC antibodies. Enhancing the capacity of NK cells to mediate ADCC could assist in controlling influenza virus infections.

journal_name

J Virol

journal_title

Journal of virology

authors

Jegaskanda S,Vanderven HA,Tan HX,Alcantara S,Wragg KM,Parsons MS,Chung AW,Juno JA,Kent SJ

doi

10.1128/JVI.02090-18

subject

Has Abstract

pub_date

2019-02-19 00:00:00

issue

eissn

0022-538X

issn

1098-5514

pii

JVI.02090-18

journal_volume

pub_type

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Influenza Virus Infection Enhances Antibody-Mediated NK Cell Functions via Type I Interferon-Dependent Pathways.