Immunoregulation and the Role of IL-17 During Chronic Pulmonary Exposure to Aspergillus fumigatus.

Abstract

Aspergillus fumigatus is an opportunistic fungal pathogen whose spores – conidia – are inhaled at a rate of several hundred per day but pose little threat to immunocompetent individuals. A. fumigatus has been implicated in a number of allergic airway responses including allergic bronchopulmonary aspergillosis and asthma. Repeated intranasal exposure to A. fumigatus conidia in C57BL/6 mice results in a pulmonary hypersensitivity response characterized by inflammation, eosinophilia, and Th2 cytokine production. We find that this hypersensitivity is preceded by an initial regulatory response, and further challenges result in an emergent Th17 response. IL-17 exacerbates acute inflammation by enhancing eosinophil trafficking but does not completely abrogate the hypersensitivity response. In addition, lack of IL-17 production reduces the initial regulatory response and enhances fungal clearance from the lungs. Together, these results suggest that IL-17 may play a central role in the initiation and resolution of pulmonary allergic responses and could be a viable target for clinical therapies.