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

Marsh, E. K., Prestwich, E. C., Williams, L., Hart, A. R., Muir, C. F., Parker, L. C., Jonker, M. R., Heijink, I. H., Timens, W., Fife, M., Hussell, T., Hershenson, M. B., Bentley, J. K., Sun, S-C., Barksby, B. S., Borthwick, L. A., Stewart, J. P., Sabroe, I., Dockrell, D. H. & Marriott, H. M., 31-Aug-2020, In : Frontiers in Cellular and Infection Microbiology. 10, 14 p., 456.

Research output: Contribution to journalArticleAcademicpeer-review

  • Elizabeth K. Marsh
  • Elizabeth C. Prestwich
  • Lynne Williams
  • Amber R. Hart
  • Clare F. Muir
  • Lisa C. Parker
  • Marnix R. Jonker
  • Irene H. Heijink
  • Wim Timens
  • Mark Fife
  • Tracy Hussell
  • Marc B. Hershenson
  • J. Kelley Bentley
  • Shao-Cong Sun
  • Ben S. Barksby
  • Lee A. Borthwick
  • James P. Stewart
  • Ian Sabroe
  • David H. Dockrell
  • Helen M. 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.

Original languageEnglish
Article number456
Number of pages14
JournalFrontiers in Cellular and Infection Microbiology
Volume10
Publication statusPublished - 31-Aug-2020

    Keywords

  • Pellino-1, influenza A virus, rhinovirus, COPD, asthma, airway epithelia, inflammation, IFN-GAMMA, IDENTIFICATION, PATHOGENESIS, EXPRESSION, INDUCTION, IMMUNITY

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