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

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) infect...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-07, Vol.24 (15), p.12220
Main Authors: Mohamed, Adham Abuelola, Soler, Sofía, Wegner, Julia, Bartok, Eva, Stankovic, Sanda, Brooks, Andrew G, Schlee, Martin
Format: Article
Language:English
Subjects:
Acids
Antiviral agents
Apoptosis
B cells
Belgium
Cells
CRISPR
Cytokines
Cytotoxicity
Diseases
Flow cytometry
Germany
Health aspects
Infections
Influenza
Interferon
International economic relations
Killer cells
Ligands
Phosphorylation
Respiratory syncytial virus
RNA
Scientific equipment and supplies industry
United States
Viral infections
Viruses
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241512220