Pneumologie 2015; 69 - A27
DOI: 10.1055/s-0035-1556619

Characterization of the pulmonary immune response to Aspergillus fumigatus allergen in juvenile mice with reduced mucus clearance due to airway surface dehydration

C van Bodegom 1, 2, J Schatterny 1, 2, S Hirtz 1, 2, MA Mall 1, 2, B Fritzsching 1, 2
  • 1Department of Translational Pulmonology and Division of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center, Department of Pediatrics, University of Heidelberg, Germany
  • 2Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research, Heidelberg, Germany

Introduction:

We have previously demonstrated that juvenile mice with airway overexpression of epithelial Na+ channels (βENaC-Tg) exhibit airway surface dehydration and eosinophilic airway inflammation (Mall MA, AmJRespirCritCareMed2008). We hypothesized that airway surface dehydration may increase the susceptibility for allergic airway inflammation towards Aspergillus fumigatus allergen (Af) and set out to characterize the innate and adaptive immune response in lungs during allergen challenge.

Methods:

βENaC-Tg mice were intratracheally challenged with Af. Airway inflammation was analyzed by differential cell counts from BAL and airway hyperresponsiveness (AHR) was determined by metacholine exposure and lung function. Leukocytes derived from lungs and spleens were analyzed by 11-color-flow-cytometry. Restimulation of leukocytes in vitro allowed quantification of different cytokine producing subpopulations (IL-4, IL-13, IL-10, IL-17, IFN-γ).

Results:

Intrapulmonary Af exposure significantly increased airway eosinophils and AHR in βENaC-Tg mice. Further analysis revealed significant higher pulmonary numbers for Th2, natural FOXP3+Treg and Tr1 but not for B-cells and Th17-cells in βENaC-Tg mice with Af. Without Af significantly more macrophages and ILC2-cells produced IL-13 with upregulation of alternative M2-markers in βENaC-Tg mice, which was hardly further increased in response to Af. Analysis of spleen leukocytes revealed limitation of allergic inflammation to the lung.

Conclusion:

We conclude that airway surface dehydration increased levels of IL-13 producing innate cells together with spontaneous eosinophilic airway inflammation and AHR. Exposure with Af evoked increased lung infiltration of Th2 cells and aggravated both airway inflammation and AHR. Intrapulmonary expansion of natural FOXP3+ Treg might confer limitation of the allergic immune response to the lung.

*Presenting author