Respiratory Influenza A Virus Infection Triggers Local and Systemic Natural Killer Cell Activation via Toll-Like Receptor 7

Frontiers in Immunology
Sabine Stegemann-KoniszewskiDunja Bruder

Abstract

The innate immune system senses influenza A virus (IAV) through different pathogen-recognition receptors including Toll-like receptor 7 (TLR7). Downstream of viral recognition natural killer (NK) cells are activated as part of the anti-IAV immune response. Despite the known decisive role of TLR7 for NK cell activation by therapeutic immunostimulatory RNAs, the contribution of TLR7 to the NK cell response following IAV infection has not been addressed. We have analyzed lung cytokine responses as well as the activation, interferon (IFN)-γ production, and cytotoxicity of lung and splenic NK cells following sublethal respiratory IAV infection in wild-type and TLR7ko mice. Early airway IFN-γ levels as well as the induction of lung NK cell CD69 expression and IFN-γ production in response to IAV infection were significantly attenuated in TLR7-deficient hosts. Strikingly, respiratory IAV infection also primed splenic NK cells for IFN-γ production, degranulation, and target cell lysis, all of which were fully dependent on TLR7. At the same time, lung type I IFN levels were significantly reduced in TLR7ko mice early following IAV infection, displaying a potential upstream mechanism of the attenuated NK cell activation observed. Taken tog...Continue Reading

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Citations

Nov 16, 2018·Journal of Virology·Kendra A BusseyMelanie M Brinkmann
Jul 10, 2020·European Journal of Clinical Investigation·Elisa GremeseGianfranco Ferraccioli
Jul 12, 2019·Frontiers in Immunology·Jingjing Cong, Haiming Wei
May 8, 2020·Viruses·Hi Eun Jung, Heung Kyu Lee
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Oct 16, 2021·Briefings in Functional Genomics·Megan HayIsis Ricaño-Ponce

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Methods Mentioned

BETA
bronchoalveolar
lavage
enzyme-linked immunosorbent assay
flow cytometry
bronchoalveolar lavage
PMA
FCS

Software Mentioned

GraphPad Prism
Tree Star
FlowJo

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