TLR ligands of ryegrass pollen microbial contaminants enhance Th1 and Th2 responses and decrease induction of Foxp3hi regulatory T cells

Mittag, Diana, Varese, Nirupama, Scholzen, Anja, Mansell, Ashley, Barker, Gillian, Rice, Gregory, Rolland, Jennifer M. and O'Hehir, Robyn E. (2013) TLR ligands of ryegrass pollen microbial contaminants enhance Th1 and Th2 responses and decrease induction of Foxp3hi regulatory T cells. European Journal of Immunology, 43 3: 723-733. doi:10.1002/eji.201242747

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Author Mittag, Diana
Varese, Nirupama
Scholzen, Anja
Mansell, Ashley
Barker, Gillian
Rice, Gregory
Rolland, Jennifer M.
O'Hehir, Robyn E.
Title TLR ligands of ryegrass pollen microbial contaminants enhance Th1 and Th2 responses and decrease induction of Foxp3hi regulatory T cells
Journal name European Journal of Immunology   Check publisher's open access policy
ISSN 0014-2980
1521-4141
Publication date 2013-03
Sub-type Article (original research)
DOI 10.1002/eji.201242747
Open Access Status
Volume 43
Issue 3
Start page 723
End page 733
Total pages 11
Place of publication Weinheim, Germany
Publisher Wiley - V C H Verlag
Collection year 2014
Language eng
Abstract Microbial contamination of grass pollens could affect sensitization, subsequent allergic response, and efficacy of allergen-specific immunotherapy. We investigated whether bacterial immunomodulatory substances can direct PBMC responses of allergic and nonatopic subjects against ryegrass pollen (RGP) toward Th1, Th2, or regulatory T (Treg) cells. Aqueous extracts of RGP with high or low LPS were fractionated into large and small molecular weight (MW) components by diafiltration. CFSE-labeled PBMCs from allergic and nonatopic subjects were stimulated with RGP extracts (RGPEs) and analyzed for cytokine secretion and T-cell responses. High LPS RGPE increased IFN-γ+ Th1 and IL-4+ Th2 effector cell induction and consistently decreased CD4+Foxp3hi Treg-cell induction. IL-10-producing T-cell frequency was unaltered, but IL-10 secretion was increased by high LPS RGPE. RGPE-stimulation of TLR-transfected cell lines revealed that high LPS pollen also contained a TLR2-ligand, and both batches a TLR9-ligand. Beta-1,3-glucans were detected in large and small MW fractions and were also T-cell stimulatory. In conclusion, coexposure to allergen and proinflammatory microbial stimuli does not convert an established Th2- into a Th1-response. Instead, proinflammatory responses are exacerbated and Foxp3hi Treg-cell induction is decreased. These findings show that adjuvants for specific immunotherapy should enhance Treg cells rather than target immune deviation from Th2 to Th1.
Keyword Allergology
Immune regulation
Immunotherapy
T helper cells
Toll like receptors
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
 
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Created: Wed, 27 Nov 2013, 13:34:33 EST by Anthony Yeates on behalf of UQ Centre for Clinical Research