Rhinovirus stimulated IFN-α production: how important are plasmacytoid DCs, monocytes and endosomal pH?

Xi, Yang, Finlayson, Arvid, White, Oliva J., Carroll, Melanie L. and Upham, John W. (2015) Rhinovirus stimulated IFN-α production: how important are plasmacytoid DCs, monocytes and endosomal pH?. Clinical and Translational Immunology, 4 10: . doi:10.1038/cti.2015.27

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
cti201527a.pdf Full text (open access) application/pdf 1.83MB 0

Author Xi, Yang
Finlayson, Arvid
White, Oliva J.
Carroll, Melanie L.
Upham, John W.
Title Rhinovirus stimulated IFN-α production: how important are plasmacytoid DCs, monocytes and endosomal pH?
Journal name Clinical and Translational Immunology   Check publisher's open access policy
ISSN 2050-0068
Publication date 2015-10-30
Sub-type Article (original research)
DOI 10.1038/cti.2015.27
Open Access Status DOI
Volume 4
Issue 10
Total pages 8
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract Human rhinovirus (HRV) infection is a major cause of asthma exacerbations, which appears to be linked to a defective innate immune response to infection. Although the type I interferons (IFN-α and IFN-β) have a critical role in protecting against most viral infections, the cells responsible for IFN production in response to HRV and the relative importance of pattern recognition receptors located in endosomes has not been fully elucidated. In the current study we demonstrate that, using intracellular flow cytometry, >90% of the IFN-α-producing cells in human blood mononuclear cells following HRV16 exposure are plasmacytoid dendritic cells, whereas monocytes and myeloid dendritic cells contribute only 10% and <1%, respectively, of the IFN-α production. Bafilomycin and chloroquine, agents that inhibit the function of endosomal toll-like receptors (TLRs), significantly reduced the capacity of TLR3-, TLR7- and TLR-9-stimulated cells to produce IFN-α and the IFN-induced chemokine CXCL10 (IP-10). In contrast, only bafilomycin (but not chloroquine) effectively suppressed HRV16-stimulated IFN-α and IP-10 production, whereas neither bafilomycin or chloroquine inhibited HRV16-stimulated interleukin-6 release. Attempts to block IFN-α production with commercially available TLR-specific oligonucleotides were unsuccessful due to major ‘off-target’ effects. These findings suggest that among circulating haemopoietic cells, plasmacytoid dendritic cells and TLRs located within endosomes are critical for inducing efficient IFN-I production in response to HRVs.
Keyword Antiviral immunity
Endosomes
Human rhinovirus
Plasmacytoid dendritic cells
Type I interferons
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: Google Scholar Search Google Scholar
Created: Thu, 06 Apr 2017, 12:48:04 EST by Camilla Xi on behalf of UQ Diamantina Institute