TY - JOUR T1 - Late-breaking abstract: House dust mite triggering of Dectin-2 is critical for the initiation of allergic airway inflammation JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - 3411 AU - Deborah Clarke AU - Martyn Foster AU - Nicola Davis AU - Stephanie Heasman AU - Arthur Lewis AU - Ian Anderson AU - Matthew Sleemam AU - Richard May AU - Matthew Robinson Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/3411.abstract N2 - Introduction: How the immune system senses aeroallergens and triggers an aberrant inflammation is poorly understood. Dectin-2 is a house dust mite (HDM)-sensing pattern recognition receptor, and its expression on dendritic cells is required for the Th2-skewed adaptive response to HDM.Objective: To define the role of Dectin-2 in HDM-induced allergic airway inflammation and its expression in biopsies from asthmatic patients.Results: In a 3 week mouse model of repeated intranasal HDM challenge, prophylactic antibody blockade of Dectin-2 potently attenuated the characteristic allergic inflammation and airway hyperresponsiveness. Anti-Dectin-2 did not reduce the inflammation once established, but did prevent neutrophil influx following a single HDM challenge. Together these data suggest a non-redundant role for Dectin-2 in the initiation of the HDM response.To define the mechanism by which Dectin-2 triggers HDM-induced inflammation, we conducted ex vivo experiments using cultured alveolar macrophages. These indicated that Dectin-2 was necessary for the induction of cysteinyl leukotrienes, as reported for dendritic cells, but not chemokines or cytokines. Furthermore we demonstrated in our single challenge model that zileuton, an inhibitor of leukotriene production, produced a similar effect as Dectin-2 blockade.Finally we found a marked increase in the number of Dectin-2 positive cells in bronchial biopsies from asthmatic subjects when compared to normal controls.Conclusions: Alveolar macrophage sensing of HDM by Dectin-2 elicits the production of cysteinyl leukotrienes, and this axis is key for the initiation of allergic airway inflammation. Dectin-2 is associated with asthma. ER -