The secretome profiling of a pediatric airway epithelium infected with hRSV identified aberrant apical/basolateral trafficking and novel immune modulating (CXCL6, CXCL16, CSF3) and antiviral (CEACAM1) proteins.

Olivier Touzelet, Lindsay Broadbent, Stuart D Armstrong, Aljabr Waleed, Elaine Cloutman-Green, Ultan Power*, Julian A Hiscox*

*Corresponding author for this work

Research output: Contribution to conferencePaper

Abstract

The respiratory epithelium comprises polarized cells at the interface between the environment and airway tissues. Polarized apical and basolateral protein secretions are a feature of airway epithelium homeostasis. Human respiratory syncytial virus (hRSV) is a major human pathogen that primarily targets the respiratory epithelium. However, the consequences of hRSV infection on epithelium secretome polarity and content remain poorly understood. To investigate the hRSV-associated apical and basolateral secretomes, a proteomics approach was combined with an ex-vivo pediatric human airway epithelial (HAE) model of hRSV infection (data are available via ProteomeXchange with identifier PXD013661). Following infection, a skewing of apical/basolateral abundance ratios was identified for several individual proteins. Novel modulators of neutrophil and lymphocyte activation (CXCL6, CSF3, SECTM1 or CXCL16), and antiviral proteins (BST2 or CEACAM1) were detected in infected, but not in uninfected cultures. Importantly, CXCL6, CXCL16, CSF3 were also detected in nasopharyngeal aspirates (NPA) from hRSV-infected infants but not healthy controls. Furthermore, the antiviral activity of CEACAM1 against RSV was confirmed in vitro using BEAS-2B cells.hRSV infection disrupted the polarity of the pediatric respiratory epithelial secretome and was associated with immune modulating proteins (CXCL6, CXCL16, CSF3) never linked with this virus before. In addition, the antiviral activity of CEACAM1 against hRSV had also never been previously characterized. This study, therefore, provides novel insights into RSV pathogenesis and endogenous antiviral responses in pediatric airway epithelium.
Original languageEnglish
Publication statusPublished - 12 Apr 2019
EventMicrobiology Society annual meeting 2019 - Belfast
Duration: 08 Apr 201911 Apr 2019

Seminar

SeminarMicrobiology Society annual meeting 2019
CityBelfast
Period08/04/201911/04/2019

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