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

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

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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
Pages (from-to)1-14
Number of pages14
JournalFrontiers in Cellular and Infection Microbiology
Volume10
DOIs
Publication statusPublished - 31 Aug 2020

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins
  • Picornaviridae Infections
  • Pulmonary Disease, Chronic Obstructive
  • Rhinovirus
  • Ubiquitin-Protein Ligases/genetics
  • Virus Diseases

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