Th2 cells promote eosinophil-independent pathology in a murine model of allergic bronchopulmonary aspergillosis

Repeated inhalation of airborne conidia derived from the fungusAspergillus 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 T cell-derived IL-4/IL-13 for induction of allergic lung inflammation. Selective deletion of IL-4/IL-13 in T cells blunted theAf-induced lung eosinophilia and further resulted in lower expression of STAT6-regulated chemokines and effector proteins such as Arginase 1, Relm-alpha, Relm-beta, and Muc5a/c. Eosinophil-deficient Delta dblGata 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 betweenAf-challenged Delta dblGata and WT mice. Based on these results, we conclude that T cell-derived IL-4/IL-13 is essential forAf-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.