Pollen metabolome analysis reveals adenosine as a major regulator of dendritic cell–primed TH cell responses

Gilles, Stefanie; Fekete, Ágnes; Zhang, Xin; Beck, Isabelle; Blume, Cornelia; Ring, Johannes; Schmidt‐Weber, Carsten B.; Behrendt, Heidrun; Schmitt‐Kopplin, Philippe; Traidl‐Hoffmann, Claudia

doi:10.1016/j.jaci.2010.12.1082

Cited by 63 publications

(67 citation statements)

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“…In this context, pollens, beside allergens, contain a range of other compounds that may be contributing to initiation, manifestation, or exacerbation of allergic inflammation. Adjuvant factors of pollens include: 1) NAD(P)H-oxidases that generate reactive oxygen species provide a signal that enhances allergic airway inflammation (21); 2) bioactive lipid mediators (PALMS), with chemical and functional similari- ties to leukotrienes and PGs, that contribute to the generation of a local microenvironment favoring T H2 responses (22); and 3) adenosine, a potent immunoregulator in pollen allergy, that acts on the level of dendritic cells (23). If such compounds are present in pollensomes, they will likely contribute to allergen sensitization and clinic symptoms.…”

Section: Discussionmentioning

confidence: 99%

Pollensomes as Natural Vehicles for Pollen Allergens

Prado

Linares

Sánz

et al. 2015

The Journal of Immunology

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Olive (Olea europaea) pollen constitutes one of the most important allergen sources in the Mediterranean countries and some areas of the United States, South Africa, and Australia. Recently, we provided evidence that olive pollen releases nanovesicles of respirable size, named generically pollensomes, during in vitro germination. Olive pollensomes contain allergens, such as Ole e 1, Ole e 11, and Ole e 12, suggesting a possible role in allergy. The aim of this study was to assess the contribution of pollensomes to the allergic reaction. We show that pollensomes exhibit allergenic activity in terms of patients’ IgE-binding capacity, human basophil activation, and positive skin reaction in sensitized patients. Furthermore, allergen-containing pollensomes have been isolated from three clinically relevant nonphylogenetically related species: birch (Betula verrucosa), pine (Pinus sylvestris), and ryegrass (Lolium perenne). Most interesting, pollensomes were isolated from aerobiological samples collected with an eight-stage cascade impactor collector, indicating that pollensomes secretion is a naturally occurring phenomenon. Our findings indicate that pollensomes may represent widespread vehicles for pollen allergens, with potential implications in the allergic reaction.

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Section: Discussionmentioning

confidence: 99%

Pollensomes as Natural Vehicles for Pollen Allergens

Prado

Linares

Sánz

et al. 2015

The Journal of Immunology

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“…Pollen grains release more immunologically active compounds than only allergen, like PALMS, adenosine and NADPH oxidase (Dharajiya et al, 2007;Gilles et al, 2009Gilles et al, , 2011. These compounds can act as adjuvants, however the allergen from pollen is the dominant factor for evoking symptoms (Brito et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Release of Bet v 1 from birch pollen from 5 European countries. Results from the HIALINE study

Buters

Thibaudon

Smith

et al. 2012

Atmospheric Environment

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“…The peanut allergen Ara h 1 is a ligand for the carbohydrate receptor DC-SIGN that facilitates Ara h 1 uptake by DCs [9]. Birch pollen-derived substances, such as phytoprostanes and adenosine, can bias immune responses toward Th2 via modulation of DCs [10,11].…”

Section: Introductionmentioning

confidence: 99%

TLR ligands of ryegrass pollen microbial contaminants enhance Th1 and Th2 responses and decrease induction of Foxp3^hi regulatory T cells

et al. 2013

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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 + Foxp3 hi 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 Foxp3 hi 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. Keywords: Allergology r Immune regulation r Immunotherapy r T helper cells r Toll like receptorsAdditional supporting information may be found in the online version of this article at the publisher's web-siteCorrespondence: Dr. Diana Mittag e-mail: dianamittag@gmail.com IntroductionA combination of genetic predisposition and environmental factors determines the development of immune-mediated inflammatory diseases including allergy and asthma [1][2][3]. An important environmental factor is exposure to microbial compounds such The role of exposure to microbes in allergic sensitization has been studied extensively in the context of the hygiene hypothesis, which states that high exposure to particular microbes protects against development of Th2-based disease. In murine studies, low levels of LPS enhanced Th2-type responses to inhaled antigens and high LPS doses favored a Th1 response [12]. The incidence of allergic sensitization is inversely correlated with level of exposure to LPS in children with a particular single nucleotide polymorphism in the CD14 promoter region [13]. Conversely, LPS found on pollen grains due to Gram-negative bacterial contamination has been suggested to facilitate sensitization to pollen allergens as well as aggravate allergic responses in already sensitized individuals [14].Microbial contaminants in allergen extracts are also likely to affect efficacy of allergen-specific immunotherapy (SIT), potentially in different ways. SIT is the only curative treatment for allergy and involves subcutaneous injection of increasing doses of aller...

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Pollen metabolome analysis reveals adenosine as a major regulator of dendritic cell–primed TH cell responses

Cited by 63 publications

References 36 publications

Pollensomes as Natural Vehicles for Pollen Allergens

Pollensomes as Natural Vehicles for Pollen Allergens

Release of Bet v 1 from birch pollen from 5 European countries. Results from the HIALINE study

TLR ligands of ryegrass pollen microbial contaminants enhance Th1 and Th2 responses and decrease induction of Foxp3^hi regulatory T cells

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Pollen metabolome analysis reveals adenosine as a major regulator of dendritic cell–primed TH cell responses

Cited by 63 publications

References 36 publications

Pollensomes as Natural Vehicles for Pollen Allergens

Pollensomes as Natural Vehicles for Pollen Allergens

Release of Bet v 1 from birch pollen from 5 European countries. Results from the HIALINE study

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

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TLR ligands of ryegrass pollen microbial contaminants enhance Th1 and Th2 responses and decrease induction of Foxp3^hi regulatory T cells