AUTHOR=Marsh Elizabeth K. , Prestwich Elizabeth C. , Williams Lynne , Hart Amber R. , Muir Clare F. , Parker Lisa C. , Jonker Marnix R. , Heijink Irene H. , Timens Wim , Fife Mark , Hussell Tracy , Hershenson Marc B. , Bentley J. Kelley , Sun Shao-Cong , Barksby Ben S. , Borthwick Lee A. , Stewart James P. , Sabroe Ian , Dockrell David H. , Marriott Helen M. TITLE=Pellino-1 Regulates the Responses of the Airway to Viral Infection JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=10 YEAR=2020 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.00456 DOI=10.3389/fcimb.2020.00456 ISSN=2235-2988 ABSTRACT=

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.