Therapeutic modality of plasmacytoid dendritic cells in a murine model of <em>Aspergillus fumigatus</em> sensitized and infected asthma

Abstract

Aspergillus fumigatus (Af) is a representative pathogen for severe asthma with fungal sensitization (SAFS), which has been coined to define a particular phenotype of severe asthma despite the use of high-dose inhaled corticosteroids and long-acting bronchodilators. Since current therapies cannot adequately control SAFS, a new therapeutic modality is required. Focusing on the immunoregulatory profile of plasmacytoid dendritic cells (pDCs), the purpose of the present study was to investigate the effects of intranasal transfer of pDCs to a murine model of Af sensitized and infected asthma mimicking SAFS on airway inflammation and cytokine profiles. Splenic pDCs were obtained from Af sensitized and infected donor mice. Thereafter, these pDCs were intranasally transferred into the airway of Af sensitized and infected recipient mice. pDCs inhibited both eosinophilic and neutrophilic airway inflammation. Analysis of cytokine profiles in lung tissue revealed that pDCs significantly inhibited proinflammatory cytokines, MIP-2, IL-5 and IL-17, and significantly increased an immunoregulatory cytokine, IL-10. In contrast, pDCs did not significantly modulate IFN-γ, a critical cytokine for antifungal immunity, suggesting the absence of immunosuppressive effects. Transfer of pDCs into the airway could be an effective and safe therapeutic modality for SAFS.

Keywords

• severe asthma with fungal sensitization
• <em>Aspergillus fumigates</em>
• plasmacytoid dendritic cells
• airway inflammation
• cytokines