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

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Abstract

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 T H 2-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. © 2009 American Academy of Allergy, Asthma & Immunology.

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APA

Nathan, A. T., Peterson, E. A., Chakir, J., & Wills-Karp, M. (2009). Innate immune responses of airway epithelium to house dust mite are mediated through β-glucan-dependent pathways. Journal of Allergy and Clinical Immunology, 123(3), 612–618. https://doi.org/10.1016/j.jaci.2008.12.006

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