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lüll Dectin-2 sensing of house dust mite is critical for the initiation of airway inflammation Clarke DL; Davis NH; Campion CL; Foster ML; Heasman SC; Lewis AR; Anderson IK; Corkill DJ; Sleeman MA; May RD; Robinson MJMucosal Immunol 2014[May]; 7 (3): 558-67How 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. In a 3-week mouse model of repeated intranasal HDM challenge, anti-Dectin-2 potently attenuated the characteristic allergic inflammation and airway hyper-responsiveness. Anti-Dectin-2 also prevented neutrophil influx following a single HDM challenge. Interestingly, cysteinyl leukotrienes, but not chemokine and cytokine levels were inhibited by anti-Dectin-2 in this acute model, and in ex vivo challenge of cultured alveolar macrophages with HDM. Furthermore in the single-challenge model, zileuton, an inhibitor of leukotriene production, produced a similar effect as Dectin-2 blockade. Together these data suggest alveolar macrophage sensing of HDM by Dectin-2 elicits the production of cysteinyl leukotrienes, and this axis is key for the initiation of airway inflammation to this aeroallergen. Finally, we found Dectin-2-positive infiltrating cells present in bronchial biopsies from asthmatic subjects.|Allergens/immunology[MESH]|Animals[MESH]|Antibodies, Neutralizing/immunology/pharmacology[MESH]|Antibodies/immunology/pharmacology[MESH]|Antigens, Dermatophagoides/*immunology[MESH]|Asthma/*immunology/metabolism[MESH]|Cytokines/metabolism[MESH]|Disease Models, Animal[MESH]|Female[MESH]|Humans[MESH]|Inflammation/immunology/metabolism[MESH]|Lectins, C-Type/antagonists & inhibitors/*immunology/metabolism[MESH]|Leukotrienes/biosynthesis[MESH]|Lung/immunology/metabolism[MESH]|Macrophages, Alveolar/immunology/metabolism[MESH]|Mice[MESH]|Neutrophils/immunology/metabolism[MESH]|Pyroglyphidae/*immunology[MESH]|Respiratory Hypersensitivity/immunology/metabolism[MESH] |