title: Dectin-2 sensing of house dust mite is critical for the initiation of airway inflammation.
abstract: 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. 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.
authors.affiliation: Departments of Respiratory, Inflammation and Autoimmunity, MedImmune Ltd, Cambridge, UK.
authors.forename: D L
authors.initials: DL
authors.lastname: Clarke
authors.affiliation: Departments of Respiratory, Inflammation and Autoimmunity, MedImmune Ltd, Cambridge, UK.
authors.forename: N H E
authors.initials: NH
authors.lastname: Davis
authors.affiliation: Departments of Respiratory, Inflammation and Autoimmunity, MedImmune Ltd, Cambridge, UK.
authors.forename: C L
authors.initials: CL
authors.lastname: Campion
authors.affiliation: Department of Pathology, Safety Assessment UK, AstraZeneca R&D, Loughborough, UK.
authors.forename: M L
authors.initials: ML
authors.lastname: Foster
authors.affiliation: Research Histology, MedImmune Ltd, Cambridge, UK.
authors.forename: S C
authors.initials: SC
authors.lastname: Heasman
authors.affiliation: Research Histology, MedImmune Ltd, Cambridge, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Lewis
authors.affiliation: 1] Departments of Respiratory, Inflammation and Autoimmunity, MedImmune Ltd, Cambridge, UK [2] Present address: Johnson & Johnson, London, UK.
authors.forename: I K
authors.initials: IK
authors.lastname: Anderson
authors.affiliation: Departments of Respiratory, Inflammation and Autoimmunity, MedImmune Ltd, Cambridge, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Corkill
authors.affiliation: Departments of Respiratory, Inflammation and Autoimmunity, MedImmune Ltd, Cambridge, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Sleeman
authors.affiliation: Departments of Respiratory, Inflammation and Autoimmunity, MedImmune Ltd, Cambridge, UK.
authors.forename: R D
authors.initials: RD
authors.lastname: May
authors.affiliation: Departments of Respiratory, Inflammation and Autoimmunity, MedImmune Ltd, Cambridge, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Robinson
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D015289:Leukotrienes / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D039981:Pyroglyphidae / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D000906:Antibodies; D057134:Antibodies, Neutralizing; D039741:Antigens, Dermatophagoides; C000593630:CLEC6A protein, human; D016207:Cytokines; D037181:Lectins, C-Type; D015289:Leukotrienes; C445340:dectin-2, mouse