Human rhinovirus-induced inflammatory responses are inhibited by phosphatidylserine containing liposomes

CA Stokes, R Kaur, MR Edwards, M Mondhe, D Robinson, EC Prestwich, RD Hume, CA Marshall, Y Perrie, VB O'Donnell, JL Harwood, I Sabroe, LC Parker

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Abstract

Human rhinovirus (HRV) infections are major contributors to the healthcare burden associated with acute exacerbations of chronic airway disease, such as chronic obstructive pulmonary disease and asthma. Cellular responses to HRV are mediated through pattern recognition receptors that may in part signal from membrane microdomains. We previously found Toll-like receptor signaling is reduced, by targeting membrane microdomains with a specific liposomal phosphatidylserine species, 1-stearoyl-2-arachidonoyl-sn-glycero-3-phospho-L-serine (SAPS). Here we explored the ability of this approach to target a clinically important pathogen. We determined the biochemical and biophysical properties and stability of SAPS liposomes and studied their ability to modulate rhinovirus-induced inflammation, measured by cytokine production, and rhinovirus replication in both immortalized and normal primary bronchial epithelial cells. SAPS liposomes rapidly partitioned throughout the plasma membrane and internal cellular membranes of epithelial cells. Uptake of liposomes did not cause cell death, but was associated with markedly reduced inflammatory responses to rhinovirus, at the expense of only modest non-significant increases in viral replication, and without impairment of interferon receptor signaling. Thus using liposomes of phosphatidylserine to target membrane microdomains is a feasible mechanism for modulating rhinovirus-induced signaling, and potentially a prototypic new therapy for viral-mediated inflammation.Mucosal Immunology advance online publication, 24 February 2016; doi:10.1038/mi.2015.137.

Original languageEnglish
Number of pages14
JournalMucosal Immunology
Early online date24 Feb 2016
DOIs
Publication statusE-pub ahead of print - 24 Feb 2016

Keywords

  • human rhinovirus
  • healthcare
  • inflammatory response

Cite this

Stokes, CA., Kaur, R., Edwards, MR., Mondhe, M., Robinson, D., Prestwich, EC., Hume, RD., Marshall, CA., Perrie, Y., O'Donnell, VB., Harwood, JL., Sabroe, I., & Parker, LC. (2016). Human rhinovirus-induced inflammatory responses are inhibited by phosphatidylserine containing liposomes. Mucosal Immunology. https://doi.org/10.1038/mi.2015.137