Dectin-2 sensing of house dust mite is critical for the initiation of airway inflammation

Mucosal Immunol. 2014 May;7(3):558-67. doi: 10.1038/mi.2013.74. Epub 2013 Oct 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology
  • Animals
  • Antibodies / immunology
  • Antibodies / pharmacology
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / pharmacology
  • Antigens, Dermatophagoides / immunology*
  • Asthma / immunology*
  • Asthma / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Lectins, C-Type / antagonists & inhibitors
  • Lectins, C-Type / immunology*
  • Lectins, C-Type / metabolism
  • Leukotrienes / biosynthesis
  • Lung / immunology
  • Lung / metabolism
  • Macrophages, Alveolar / immunology
  • Macrophages, Alveolar / metabolism
  • Mice
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Pyroglyphidae / immunology*
  • Respiratory Hypersensitivity / immunology
  • Respiratory Hypersensitivity / metabolism

Substances

  • Allergens
  • Antibodies
  • Antibodies, Neutralizing
  • Antigens, Dermatophagoides
  • Cytokines
  • Lectins, C-Type
  • Leukotrienes
  • dectin-2, human
  • dectin-2, mouse