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Innate immune responses of airway epithelium to house dust mite are mediated through β-glucan–dependent pathways

https://doi.org/10.1016/j.jaci.2008.12.006Get rights and content

Background

House dust mite (HDM) induces allergic asthma in sensitized individuals, although the mechanisms by which HDM is sensed and recognized by the airway mucosa, leading to dendritic cell (DC) recruitment, activation, and subsequent TH2-mediated responses, are unknown.

Objective

We sought to define the pathways by which HDM activates respiratory epithelium to induce allergic airway responses.

Methods

Using a human airway epithelial cell line (16HBE14o-), we studied secretion of the DC chemokine CCL20 after exposure to HDM or other allergens, investigated components of the HDM responsible for the induction of chemokine release, and examined activation of signaling pathways. Central findings were also confirmed in primary human bronchial cells.

Results

We demonstrate that exposure of airway epithelium to HDM results in specific and rapid secretion of CCL20, a chemokine attractant for immature DCs. The induction of CCL20 secretion is dose and time dependent and quite specific to HDM because other allergens, such as ragweed pollen and cockroach antigen, fail to significantly induce CCL20 secretion. Induction of CCL20 secretion is not protease or Toll-like receptor 2/4 dependent but, interestingly, relies on β-glucan moieties within the HDM extract, as evidenced by the ability of other β-glucans to competitively inhibit its secretion and by the fact that disruption of these structures by treatment of HDM with β-glucanase significantly reduces subsequent chemokine secretion.

Conclusion

Taken together, our results describe a novel mechanism for specific pattern recognition of HDM-derived β-glucan moieties, which initiates allergic airway inflammation and, through recruitment of DCs, might link innate pattern recognition at the airway surface with adaptive immune responses.

Section snippets

Reagents and antibodies

HDM, Der p 1, and ragweed were purchased from Greer (Lenoir, NC); protease inhibitor cocktail (1 complete Mini tablet dissolved in 25 mL of media) was purchased from Roche (Indianapolis, Ind); laminarin, ovalbumin (OVA), chitin, zymosan, curdlan, β-glucanase, and piceatannol were purchased from Sigma (St Louis Mo); cycloheximide was purchased from Calbiochem (San Diego, Calif); and LPS was purchased from Invitrogen (Carlsbad, Calif). Cockroach antigen was a gift from Dr Kristen Page

CCL20 and HDM

CCL20 is crucial for the initial recruitment of immature DCs to the lung during allergic airway responses and has been found to be upregulated by a variety of inflammatory cytokines.26, 27, 28, 29 To determine whether HDM initiates allergic airway responses at the mucosal surface, we examined the ability of HDM to induce CCL20 secretion from human respiratory epithelial cells. Specifically, we treated nearly confluent 16HBE14o- cells that were serum starved overnight with increasing

Discussion

In this study we describe a novel pattern-recognition pathway wherein the allergen HDM binds a non-Toll PRR to initiate innate immune responses. Our data show that stimulation of respiratory epithelium by HDM induces rapid secretion of CCL20, a chemokine central to recruitment of immature DCs to the lung. The effect is specific to HDM because other aeroallergens, such as ragweed and cockroach, fail to elicit this response, and the response is dependent on β-glucan structures in the HDM extract.

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    M.W.-K. received grant support from the National Institutes of Health (P01 HL076383 and R01 H667737).

    Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

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