Innate IFNs and plasmacytoid dendritic cells constrain Th2 cytokine responses to rhinovirus: A regulatory mechanism with relevance to asthma

Pritchard, Antonia L., Carroll, Melanie L., Burel, Julie G., White, Olivia J., Phipps, Simon and Upham, John W. (2012) Innate IFNs and plasmacytoid dendritic cells constrain Th2 cytokine responses to rhinovirus: A regulatory mechanism with relevance to asthma. Journal of Immunology, 188 12: 5898-5905.


Author Pritchard, Antonia L.
Carroll, Melanie L.
Burel, Julie G.
White, Olivia J.
Phipps, Simon
Upham, John W.
Title Innate IFNs and plasmacytoid dendritic cells constrain Th2 cytokine responses to rhinovirus: A regulatory mechanism with relevance to asthma
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2012-06
Sub-type Article (original research)
DOI 10.4049/jimmunol.1103507
Volume 188
Issue 12
Start page 5898
End page 5905
Total pages 8
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Collection year 2013
Language eng
Abstract Human rhinoviruses (RV) cause only minor illness in healthy individuals, but can have deleterious consequences in people with asthma. This study sought to examine normal homeostatic mechanisms regulating adaptive immunity to RV in healthy humans, focusing on effects of IFN-αβ and plasmacytoid dendritic cells (pDC) on Th2 immune responses. PBMC were isolated from 27 healthy individuals and cultured with RV16 for up to 5 d. In some experiments, IFN-αβ was neutralized using a decoy receptor that blocks IFN signaling, whereas specific dendritic cell subsets were depleted from cultures with immune-magnetic beads. RV16 induced robust expression of IFN-α, IFN-β, multiple IFN-stimulated genes, and T cell-polarizing factors within the first 24 h. At 5 d, the production of memory T cell-derived IFN-γ, IL-10, and IL-13, but not IL-17A, was significantly elevated. Neutralizing the effects of type-I IFN with the decoy receptor B18R led to a significant increase in IL-13 synthesis, but had no effect on IFN-γ synthesis. Depletion of pDC from RV-stimulated cultures markedly inhibited IFN-α secretion, and led to a significant increase in expression and production of the Th2 cytokines IL-5 (p = 0.02), IL-9 (p < 0.01), and IL-13 (p < 0.01), but had no effect on IFN-γ synthesis. Depletion of CD1c+ dendritic cells did not alter cytokine synthesis. In healthy humans, pDC and the IFN-αβ they secrete selectively constrain Th2 cytokine synthesis following RV exposure in vitro. This important regulatory mechanism may be lost in asthma; deficient IFN-αβ synthesis and/or pDC dysfunction have the potential to contribute to asthma exacerbations during RV infections.
Keyword Bronchial Epithelial-Cells
Time Rt-Pcr
Interferon-Alpha
Viral Replication
Acute Exacerbations
Allergic Subjects
Peripheral-Blood
Ige-Receptor
Virus
Infection
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online before print 18 May 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Biomedical Sciences Publications
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 14 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Access Statistics: 37 Abstract Views  -  Detailed Statistics
Created: Mon, 02 Jul 2012, 08:00:15 EST by System User on behalf of School of Biomedical Sciences