Abstract
Repeated inhalation of airborne conidia derived from the fungus Aspergillus fumigatus (Af) can lead to a severe eosinophil-dominated inflammatory condition of the lung termed allergic bronchopulmonary aspergillosis (ABPA). ABPA affects about 5 million individuals worldwide and the mechanisms regulating lung pathology in ABPA are poorly understood. Here, we used a mouse model of ABPA to investigate the role of eosinophils and Tcell-derived IL-4/IL-13 for induction of allergic lung inflammation. Selective deletion of IL-4/IL-13 in Tcells blunted the Af-induced lung eosinophilia and further resulted in lower expression of STAT6-regulated chemokines and effector proteins such as Arginase 1, Relm-α, Relm-β, and Muc5a/c. Eosinophil-deficient ΔdblGata mice showed lower IL-4 expression in the lung and the number of Th2 cells in the lung parenchyma was reduced. However, expression of the goblet cell markers Clca1 and Muc5a/c, abundance of mucin-positive cells, as well as weight gain of lungs were comparable between Af-challenged ΔdblGata and WT mice. Based on these results, we conclude that Tcell-derived IL-4/IL-13 is essential for Af-induced lung eosinophilia and inflammation while eosinophils may play a more subtle immunomodulatory role and should not simply be regarded as pro-inflammatory effector cells in ABPA.
Highlights
Allergic bronchopulmonary aspergillosis (ABPA) is a chronic inflammatory condition affecting about 5 million people worldwide with a high incidence in asthma and cystic fibrosis patients [1,2]
Basophils and ILC2s showed only a small increase in total numbers (Supporting Information Fig. 3). We conclude that this repetitive low-dose administration of Aspergillus fumigatus (Af) conidia elicits a strong type 2 immune response with massive lung eosinophilia as it is seen in human ABPA patients
Having shown that T cell-derived IL-4/IL-13 is critical for Afinduced lung and blood eosinophilia, we further investigated whether this correlates with histopathological changes and expression of effector molecules associated with allergic lung inflammation
Summary
Allergic bronchopulmonary aspergillosis (ABPA) is a chronic inflammatory condition affecting about 5 million people worldwide with a high incidence in asthma and cystic fibrosis patients [1,2]. ABPA is elicited by the omnipresent fungal opportunistic. Dependent on the host immune status Af can cause various diseases in humans. In contrast to invasive aspergillosis, which primarily affects immuno-compromised patients, ABPA is. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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