Chemotaxis and activation of human peripheral blood eosinophils induced by pollen-associated lipid mediators

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The immune response of atopic individuals against allergens is characterized by increased levels of Th2 cytokines and chemokines. However, the way in which the cytokine/chemokine profile is matched to the type of invading allergen, and why these profiles sometimes derail and lead to disease, is not well understood. We recently demonstrated that pollen modulates dendritic cell (DC) function in a way that results in an enhanced capacity to initiate Th2 responses in vitro. Here, we examined the effects of aqueous birch pollen extracts (Bet.-APE) on chemokine receptor expression and chemokine production by human monocyte-derived DCs. Bet.-APE strongly induced expression and function of CXCR4 and reduced CCR1 and CCR5 expression on immature DCs. In addition, DC treatment with Bet.-APE significantly reduced LPS-induced production of CXCL10/IP-10, CCL5/RANTES; induced CCL22/macrophage-derived chemokine; and did not significantly change release of CCL17/thymus and activation-regulated chemokine. At a functional level, Bet.-APE increased the capacity of LPS-stimulated DCs to attract Th2 cells, whereas the capacity to recruit Th1 cells was reduced. Bet.-APE significantly and dose-dependently enhanced intracellular cAMP, suggesting that water-soluble factors from pollen grains bind a Gαs-protein-coupled receptor. E1-Phytoprostanes were identified to be one player in the Th2-polarizing potential of aqueous pollen extracts. In summary, our results demonstrate that pollen itself releases regulatory mediators which generate a Th2-promoting micromilieu with preferential recruitment of Th2 cells to the site of pollen exposure.

Section: Endritic Cells (Dcs)mentioning

confidence: 99%

Immunomodulatory Mediators from Pollen Enhance the Migratory Capacity of Dendritic Cells and License Them for Th2 Attraction

Mariani

Gilles

Jakob

et al. 2007

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“…Among these are a number of bioactive lipids (5), the so-called pollen-associated lipid mediators (PALMs). 3 Hitherto existing data point to two main groups of PALMs: First, the immunostimulatory PALMs activating and stimulating cells of the innate immune system such as neutrophils and eosinophils (6,7) and, second, the immunomodulatory PALMs acting on cytokine and chemokine production of human dendritic cells (DC) skewing the immune systems toward a Type-2 dominated proallergenic immune response (8,9). The finding that PALMs activate and modulate cells of the immune system added a new, as yet unappreciated aspect to the concept of pollen as mere vehicles of allergens (10).…”

mentioning

confidence: 99%

Pollen-Derived E1-Phytoprostanes Signal via PPAR-γ and NF-κB-Dependent Mechanisms

Gilles

Mariani

Bryce

et al. 2009

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In a humid milieu such as mucosal surfaces, pollen grains do not only release allergens but also proinflammatory and immunomodulatory lipids, termed pollen-associated lipid mediators. Among these, the E1-phytoprostanes (PPE1) were identified to modulate dendritic cell (DC) function: PPE1 inhibit the DC’s capacity to produce IL-12 and enhance DC mediated TH2 polarization of naive T cells. The mechanism(s) by which PPE1 act on DC remained elusive. We thus analyzed candidate signaling elements and their role in PPE1-mediated regulation of DC function. Aqueous birch pollen extracts induced a marked cAMP response in DC that could be blocked partially by EP2 and EP4 antagonists. In contrast, PPE1 hardly induced cAMP and the inhibitory effect on IL-12 production was mostly independent of EP2 and EP4. Instead, PPE1 inhibited the LPS-induced production of IL-12 p70 by a mechanism involving the nuclear receptor PPAR-γ. Finally, PPE1 efficiently blocked NF-κB signaling in DCs by inhibiting IκB-α degradation, translocation of p65 to the nucleus, and binding to its target DNA elements. We conclude that pollen-derived PPE1 modulate DC function via PPAR-γ dependent pathways that lead to inhibition of NFκB activation and result in reduced DC IL-12 production and consecutive TH2 polarization.

“…Pollen grains release substances that have structural similarity with the inflammatory lipid mediators (12,13). Lipid fractions from birch and grass pollen extracts induce chemotaxis and the activation of neutrophils (14) and eosinophils (15). Pollen extracts of birch, hazel, lilac, maple, and mugwort and birch pollen phytoprostanes inhibit LPS-induced IL-12 production (16) and birch pollen extract, and phytoprostanes enhance migratory and Th2-attracting capacities (17) in dendritic cells (DCs).…”

mentioning

confidence: 99%

Cupressaceae Pollen Grains Modulate Dendritic Cell Response and Exhibit IgE-Inducing Adjuvant Activity In Vivo

Kamijo¹,

Takai²,

Kuhara³

et al. 2009

Pollen is considered a source of not only allergens but also immunomodulatory substances, which could play crucial roles in sensitization and/or the exacerbation of allergies. We investigated how allergenic pollens from different plant species (Japanese cedar and Japanese cypress, which belong to the Cupressaceae family, and birch, ragweed, and grass) modulate murine bone marrow-derived dendritic cell (DC) responses and examined the effect of Cupressaceae pollen in vivo using mice. DCs were stimulated with pollen extracts or grains in the presence or absence of LPS. Cell maturation and cytokine production in DCs were analyzed by flow cytometry, ELISA, and/or quantitative PCR. Pollen extracts suppressed LPS-induced IL-12 production and the effect was greatest for birch and grass. Without LPS, pollen grains induced DC maturation and cytokine production without IL-12 secretion and the response, for which TLR 4 was dispensable, was greatest for the Cupressaceae family. Intranasal administration of Cupressaceae pollen in mice induced an elevation of serum IgE levels and airway eosinophil infiltration. Coadministration of ovalbumin with Cupressaceae pollen grains induced ovalbumin-specific IgE responses associated with eosinophil infiltration. The results suggest that modulation of DC responses by pollen differs among the plant families via (1) the promotion of DC maturation and cytokine production by direct contact and/or (2) the inhibition of IL-12 production by soluble factors. The strong DC stimulatory activity in vitro and IgE-inducing activity in mice support the clinical relevance of Cupressaceae pollen to allergies in humans.