Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Influenza A Infection Stimulates RIG-I and Enhances Effector Function of Primary Human NK Cells

Adham Abuelola Mohamed
ORCID logo ,
Sofia Soler
ORCID logo ,
Julia Wegner
,
Eva Bartok
ORCID logo ,
Sanda Stankovic
,
Andrew G. Brooks
,
Martin Schlee
*
Version 1 : Received: 26 June 2023 / Approved: 26 June 2023 / Online: 26 June 2023 (14:41:45 CEST)

A peer-reviewed article of this Preprint also exists.

Mohamed, A.A.; Soler, S.; Wegner, J.; Bartok, E.; Stankovic, S.; Brooks, A.G.; Schlee, M. Influenza A Infection Stimulates RIG-I and Enhances Effector Function of Primary Human NK Cells. Int. J. Mol. Sci. 2023, 24, 12220. Mohamed, A.A.; Soler, S.; Wegner, J.; Bartok, E.; Stankovic, S.; Brooks, A.G.; Schlee, M. Influenza A Infection Stimulates RIG-I and Enhances Effector Function of Primary Human NK Cells. Int. J. Mol. Sci. 2023, 24, 12220.

Abstract

Immune surveillance by natural killer (NK) cells and their recruitment to sites of inflammation renders them susceptible to viral infection, potentially modulating their effector function. Here, we analyzed innate RNA receptor signaling in NK cells downstream of direct Influenza A virus (IAV) infection and its impact on NK cell effector function. Infection of NK cells with IAV resulted in the activation of TBK1, NF-κB and subsequent type-I IFN secretion. CRISPR- generated knockouts in primary human NK cells revealed that this effect depended on the antiviral cytosolic RNA receptor RIG-I. Transfection of NK cells with synthetic 3p-dsRNA, a strong RIG-I agonist that mimics viral RNA, resulted in a similar phenotype and rendered NK cells resistant to subsequent IAV infection. Strikingly, both IAV infection and 3p-dsRNA transfection enhanced degranulation and cytokine production by NK cells when exposed to target cells. Thus, RIG-I activation in NK cells both supports their cell intrinsic viral defense and enhances their cytotoxic effector function against target cells.

Keywords

Influenza; NK cells; RIG-I; IFN-a/b; innate nucleic acid receptors

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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