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Pellino-1 Regulates the Responses of the Airway to Viral Infection

Lookup NU author(s): Ben Barksby, Dr Lee BorthwickORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© Copyright © 2020 Marsh, Prestwich, Williams, Hart, Muir, Parker, Jonker, Heijink, Timens, Fife, Hussell, Hershenson, Bentley, Sun, Barksby, Borthwick, Stewart, Sabroe, Dockrell and Marriott.Exposure to respiratory pathogens is a leading cause of exacerbations of airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Pellino-1 is an E3 ubiquitin ligase known to regulate virally-induced inflammation. We wished to determine the role of Pellino-1 in the host response to respiratory viruses in health and disease. Pellino-1 expression was examined in bronchial sections from patients with GOLD stage two COPD and healthy controls. Primary bronchial epithelial cells (PBECs) in which Pellino-1 expression had been knocked down were extracellularly challenged with the TLR3 agonist poly(I:C). C57BL/6 Peli1−/− mice and wild type littermates were subjected to intranasal infection with clinically-relevant respiratory viruses: rhinovirus (RV1B) and influenza A. We found that Pellino-1 is expressed in the airways of normal subjects and those with COPD, and that Pellino-1 regulates TLR3 signaling and responses to airways viruses. In particular we observed that knockout of Pellino-1 in the murine lung resulted in increased production of proinflammatory cytokines IL-6 and TNFα upon viral infection, accompanied by enhanced recruitment of immune cells to the airways, without any change in viral replication. Pellino-1 therefore regulates inflammatory airway responses without altering replication of respiratory viruses.

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Author(s): Marsh EK, Prestwich EC, Williams L, Hart AR, Muir CF, Parker LC, Jonker MR, Heijink IH, Timens W, Fife M, Hussell T, Hershenson MB, Bentley JK, Sun S-C, Barksby BS, Borthwick LA, Stewart JP, Sabroe I, Dockrell DH, Marriott HM

Publication type: Article

Publication status: Published

Journal: Frontiers in Cellular and Infection Microbiology

Year: 2020

Volume: 10

Print publication date: 01/08/2020

Online publication date: 31/08/2020

Acceptance date: 24/07/2020

Date deposited: 18/12/2020

ISSN (electronic): 2235-2988

Publisher: Frontiers Media S.A.

URL: https://doi.org/10.3389/fcimb.2020.00456

DOI: 10.3389/fcimb.2020.00456

PubMed id: 32984077

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