Inducible Lung Epithelial Resistance Requires Multisource Reactive Oxygen Species Generation To Protect against Viral Infections

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Carson T KirkpatrickS E Evans

Abstract

Viral pneumonias cause profound worldwide morbidity, necessitating novel strategies to prevent and treat these potentially lethal infections. Stimulation of intrinsic lung defenses via inhalation of synergistically acting Toll-like receptor (TLR) agonists protects mice broadly against pneumonia, including otherwise-lethal viral infections, providing a potential opportunity to mitigate infectious threats. As intact lung epithelial TLR signaling is required for the inducible resistance and as these cells are the principal targets of many respiratory viruses, the capacity of lung epithelial cells to be therapeutically manipulated to function as autonomous antiviral effectors was investigated. Our work revealed that mouse and human lung epithelial cells could be stimulated to generate robust antiviral responses that both reduce viral burden and enhance survival of isolated cells and intact animals. The antiviral protection required concurrent induction of epithelial reactive oxygen species (ROS) from both mitochondrial and dual oxidase sources, although neither type I interferon enrichment nor type I interferon signaling was required for the inducible protection. Taken together, these findings establish the sufficiency of lung epit...Continue Reading

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Citations

Jan 15, 2020·Proceedings of the National Academy of Sciences of the United States of America·Evelyn M Covés-DatsonDavid M Markovitz
Jul 22, 2020·BMC Microbiology·Ker-Kong ChenKazunari K Yokoyama
Aug 28, 2020·American Journal of Respiratory Cell and Molecular Biology·Shradha WaliScott E Evans
Sep 12, 2020·American Journal of Respiratory Cell and Molecular Biology·Megan N Ballinger, Ian C Davis
Jun 22, 2021·American Journal of Respiratory and Critical Care Medicine·Jezreel Pantaleón GarcíaRobert P Dickson
Nov 4, 2021·Biomedit︠s︡inskai︠a︡ khimii︠a︡·V V SalminA B Salmina
Jul 7, 2021·IUBMB Life·Helmut Sies, Fulvio Ursini

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Methods Mentioned

BETA
electrophoresis
flow cytometry
reverse transcription-PCR
transfection
protein assay

Software Mentioned

ImageJ
SPSS

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