Role of prostaglandin D2 /CRTH2 pathway on asthma exacerbation induced by Aspergillus fumigatus

Immunology. 2014 May;142(1):78-88. doi: 10.1111/imm.12234.

Abstract

Aspergillus fumigatus is often associated in asthmatic patients with the exacerbation of asthma symptoms. The pathomechanism of this phenomenon has not been fully understood. Here, we evaluated the immunological mechanisms and the role of the prostaglandin D2 / Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells (CRTH2) pathway in the development of Aspergillus-associated asthma exacerbation. We studied the effects of A. fumigatus on airway inflammation and bronchial hyper-responsiveness in a rat model of chronic asthma. Inhalation delivery of A. fumigatus conidia increased the airway eosinophilia and bronchial hyper-responsiveness in ovalbumin-sensitized, challenged rats. These changes were associated with prostaglandin D2 synthesis and CRTH2 expression in the lungs. Direct inflammation occurred in ovalbumin-sensitized, challenged animals, whereas pre-treatment with an antagonist against CRTH2 nearly completely eliminated the A. fumigatus-induced worsening of airway eosinophilia and bronchial hyper-responsiveness. Our data demonstrate that production of prostaglandin D2 followed by eosinophil recruitment into the airways via a CRTH2 receptor are the major pathogenic factors responsible for the A. fumigatus-induced enhancement of airway inflammation and responsiveness.

Keywords: Aspergillus fumigatus; CRTH2; airway responsiveness; asthma; eosinophil; prostaglandin D2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Aspergillus fumigatus / pathogenicity*
  • Asthma / immunology
  • Asthma / metabolism*
  • Asthma / microbiology
  • Asthma / physiopathology
  • Bronchial Hyperreactivity / immunology
  • Bronchial Hyperreactivity / metabolism*
  • Bronchial Hyperreactivity / microbiology
  • Bronchial Hyperreactivity / physiopathology
  • Disease Models, Animal
  • Eosinophils / immunology
  • Eosinophils / metabolism
  • Lung / drug effects
  • Lung / immunology
  • Lung / metabolism*
  • Lung / microbiology
  • Lung / physiopathology
  • Male
  • Ovalbumin
  • Prostaglandin D2 / metabolism*
  • Pulmonary Aspergillosis / immunology
  • Pulmonary Aspergillosis / metabolism*
  • Pulmonary Aspergillosis / microbiology
  • Pulmonary Aspergillosis / physiopathology
  • Pulmonary Eosinophilia / immunology
  • Pulmonary Eosinophilia / metabolism
  • Pulmonary Eosinophilia / microbiology
  • Rats
  • Rats, Wistar
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / metabolism*
  • Receptors, Prostaglandin / antagonists & inhibitors
  • Receptors, Prostaglandin / metabolism*
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • Ovalbumin
  • Prostaglandin D2
  • prostaglandin D2 receptor